Retrovirus-associated DNA sequences (abl) originally isolated from the Abelson murine leukemia virus (Ab-MuLV). The proto-oncogene abl (c-abl) codes for a protein that is a member of the tyrosine kinase family. The human c-abl gene is located at 9q34.1 on the long arm of chromosome 9. It is activated by translocation to bcr on chromosome 22 in chronic myelogenous leukemia.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
BENZOIC ACID amides.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
Piperazines are a class of heterocyclic organic compounds containing a seven-membered ring with two nitrogen atoms at positions 1 and 4, often used in pharmaceuticals as smooth muscle relaxants, antipsychotics, antidepressants, and antihistamines, but can also be found as recreational drugs with stimulant and entactogen properties.
Proto-oncogene protein bcr is a serine-threonine kinase that functions as a negative regulator of CELL PROLIFERATION and NEOPLASTIC CELL TRANSFORMATION. It is commonly fused with cellular abl protein to form BCR-ABL FUSION PROTEINS in PHILADELPHIA CHROMOSOME positive LEUKEMIA patients.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.
Agents that inhibit PROTEIN KINASES.
Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.
A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).
A specific pair of GROUP C CHROMSOMES of the human chromosome classification.
An autosomal recessive disorder of lipid metabolism. It is caused by mutation of the microsomal triglyceride transfer protein that catalyzes the transport of lipids (TRIGLYCERIDES; CHOLESTEROL ESTERS; PHOSPHOLIPIDS) and is required in the secretion of BETA-LIPOPROTEINS (low density lipoproteins or LDL). Features include defective intestinal lipid absorption, very low serum cholesterol level, and near absent LDL.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Progenitor cells from which all blood cells derive.
Thiazoles are heterocyclic organic compounds containing a sulfur atom and a nitrogen atom, which are bound by two carbon atoms to form a five-membered ring, and are widely found in various natural and synthetic substances, including some pharmaceuticals and vitamins.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
Established cell cultures that have the potential to propagate indefinitely.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)
A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.
The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
RNA present in neoplastic tissue.
A cell line derived from cultured tumor cells.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A family of microfilament proteins whose name derives from the fact that mutations in members of this protein family have been associated with WISKOTT-ALDRICH SYNDROME. They are involved in ACTIN polymerization and contain a polyproline-rich region that binds to PROFILIN, and a verprolin homology domain that binds G-ACTIN.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
An oncoprotein from the Cas NS-1 murine retrovirus that induces pre- B-CELL LYMPHOMA and MYELOID LEUKEMIAS. v-cbl protein is a tyrosine-phosphorylated, truncated form of its cellular homologue, PROTO-ONCOGENE PROTEIN C-CBL.
Serine-threonine protein kinases that relay signals from CYTOKINE RECEPTORS and are involved in control of CELL GROWTH PROCESSES; CELL DIFFERENTIATION; and APOPTOSIS.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The phase of chronic myeloid leukemia following the chronic phase (LEUKEMIA, MYELOID, CHRONIC-PHASE), where there are increased systemic symptoms, worsening cytopenias, and refractory LEUKOCYTOSIS.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A saturated 14-carbon fatty acid occurring in most animal and vegetable fats, particularly butterfat and coconut, palm, and nutmeg oils. It is used to synthesize flavor and as an ingredient in soaps and cosmetics. (From Dorland, 28th ed)
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Mapping of the KARYOTYPE of a cell.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Pyridine derivatives with one or more keto groups on the ring.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Aniline compounds, also known as aromatic amines, are organic chemicals derived from aniline (aminobenzene), characterized by the substitution of hydrogen atoms in the benzene ring with amino groups (-NH2).
Phosphoproteins are proteins that have been post-translationally modified with the addition of a phosphate group, usually on serine, threonine or tyrosine residues, which can play a role in their regulation, function, interaction with other molecules, and localization within the cell.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
A tricyclo bridged hydrocarbon.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.

Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance. (1/343)

The BCR-ABL chromosomal translocation is a central event in the pathogenesis of chronic myelogenous leukemia (CML). One of the ABL1 promoters (Pa) and the coding region of the gene are usually translocated intact to the BCR locus, but the translocated promoter appears to be silent in most cases. Recently, hypermethylation of Pa was demonstrated in CML and was proposed to mark advanced stages of the disease. To study this issue, we measured Pa methylation in CML using Southern blot analysis. Of 110 evaluable samples, 23 (21%) had no methylation, 17 (15%) had minimal (<15%) methylation, 12 (11%) had moderate methylation (15% to 25%), and 58 (53%) had high levels of methylation (>25%) at the ABL1 locus. High methylation was more frequent in advanced cases of CML. Among the 76 evaluable patients in early chronic phase (ECP), a major cytogenetic response with interferon-based therapy was observed in 14 of 34 patients with high methylation compared with 19 of 42 among the others (41% v 45%; P value not significant). At a median follow-up of 7 years, there was no significant difference in survival by ABL1 methylation category. Among patients who achieved a major cytogenetic response, low levels of methylation were associated with a trend towards improved survival, but this trend did not reach statistical significance. Thus, Pa methylation in CML is associated with disease progression but does not appear to predict for survival or response to interferon-based therapy.  (+info)

The tyrosine kinase Abl and its substrate enabled collaborate with the receptor phosphatase Dlar to control motor axon guidance. (2/343)

Genetic analysis of growth cone guidance choice points in Drosophila identified neuronal receptor protein tyrosine phosphatases (RPTPs) as key determinants of axon pathfinding behavior. We now demonstrate that the Drosophila Abl tyrosine kinase functions in the intersegmental nerve b (ISNb) motor choice point pathway as an antagonist of the RPTP Dlar. The function of Abl in this pathway is dependent on an intact catalytic domain. We also show that the Abl phosphoprotein substrate Enabled (Ena) is required for choice point navigation. Both Abl and Ena proteins associate with the Dlar cytoplasmic domain and serve as substrates for Dlar in vitro, suggesting that they play a direct role in the Dlar pathway. These data suggest that Dlar, Abl, and Ena define a phosphorylation state-dependent switch that controls growth cone behavior by transmitting signals at the cell surface to the actin cytoskeleton.  (+info)

Quantitative polymerase chain reaction for the detection of micrometastases in patients with breast cancer. (3/343)

PURPOSE: Previous reports have indicated that reverse transcriptase polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK-19) may be useful in the management of patients with breast cancer. However, the specificity of this technique is low, principally because of a high rate of false-positive results. To improve the specificity of this assay, we developed a quantitative RT-PCR methodology that enables an estimate to be made of the number of CK-19 transcripts in blood and bone marrow samples. PATIENTS AND METHODS: We examined 45 peripheral-blood samples and 30 bone marrow samples from patients with a variety of nonneoplastic conditions using nested RT-PCR for CK-19. We also examined bone marrow and peripheral-blood samples from 23 patients with primary breast cancer and peripheral-blood samples from 37 patients with metastatic breast cancer. The number of CK-19 transcripts was estimated in positive specimens by competitive PCR and normalized to the number of ABL transcripts as an internal control for the quality and quantity of cDNA. RT-PCR results were compared with the numbers of CK-19-positive cells detected by immunocytochemistry. RESULTS: Analysis of samples from patients without cancer enabled us to define an upper limit for the background ratio of CK-19 to ABL transcripts (1:1,000 for blood samples and 1:1,600 for bone marrow samples). Using these figures as cut-off points, elevated CK-19: ABL ratios were detected in peripheral-blood samples of 20 of 37 (54%) patients with metastatic breast cancer and in bone marrow samples of 14 of 23 (61%) patients with primary breast cancer. Only three of 23 (13%) primary breast cancer peripheral-blood samples and none of the control samples were positive by these criteria. Only two of 23 patients (9%) with primary breast cancer showed immunocytochemically detectable cells in the blood; 10 of 23 (43%) showed immunocytochemically detectable cells in the bone marrow. Of 36 patients with metastatic breast cancer, eight (22%) showed positive events. CONCLUSION: Quantitative RT-PCR for CK-19 detects a percentage of patients with breast cancer and may enable the progression or regression of the disease to be monitored.  (+info)

Dissecting NK cell development using a novel alymphoid mouse model: investigating the role of the c-abl proto-oncogene in murine NK cell differentiation. (4/343)

NK lymphocytes participate in both innate and adaptive immunity by their prompt secretion of cytokines including IFN-gamma, which activates macrophages, and by their ability to lyse virally infected cells and tumor cells without prior sensitization. Although these characteristics of NK cells are well documented, little is known about the genetic program that orchestrates NK development or about the signaling pathways that trigger NK effector functions. By crossing NK-deficient common gamma-chain (gammac) and recombinase activating gene (RAG)-2 mutant mice, we have generated a novel alymphoid (B-, T-, and NK-) mouse strain (RAG2/gammac) suitable for NK complementation in vivo. The role of the c-abl proto-oncogene in murine NK cell differentiation has been addressed in hemopoietic chimeras generated using RAG2/gammac mice reconstituted with c-abl-/- fetal liver cells. The phenotypically mature NK cells that developed in the absence of c-abl were capable of lysing tumor targets, recognizing "missing self," and performing Ab-dependent cellular cytotoxicity. Taken together, these results exclude any essential role for c-abl in murine NK cell differentiation in vivo. The RAG2/gammac model thereby provides a novel approach to establish a genetic map of NK cell development.  (+info)

Signal transducer and activator of transcription (STAT)5 activation by BCR/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR/ABL and is required for leukemogenesis. (5/343)

Signal transducer and activator of transcription (STAT)5 is constitutively activated in BCR/ ABL-expressing cells, but the mechanisms and functional consequences of such activation are unknown. We show here that BCR/ABL induces phosphorylation and activation of STAT5 by a mechanism that requires the BCR/ABL Src homology (SH)2 domain and the proline-rich binding site of the SH3 domain. Upon expression in 32Dcl3 growth factor-dependent myeloid precursor cells, STAT5 activation-deficient BCR/ABL SH3+SH2 domain mutants functioned as tyrosine kinase and activated Ras, but failed to protect from apoptosis induced by withdrawal of interleukin 3 and/or serum and did not induce leukemia in severe combined immunodeficiency mice. In complementation assays, expression of a dominant-active STAT5B mutant (STAT5B-DAM), but not wild-type STAT5B (STAT5B-WT), in 32Dcl3 cells transfected with STAT5 activation-deficient BCR/ABL SH3+SH2 mutants restored protection from apoptosis, stimulated growth factor-independent cell cycle progression, and rescued the leukemogenic potential in mice. Moreover, expression of a dominant-negative STAT5B mutant (STAT5B-DNM) in 32Dcl3 cells transfected with wild-type BCR/ABL inhibited apoptosis resistance, growth factor-independent proliferation, and the leukemogenic potential of these cells. In retrovirally infected mouse bone marrow cells, expression of STAT5B-DNM inhibited BCR/ABL-dependent transformation. Moreover, STAT5B-DAM, but not STAT5B-WT, markedly enhanced the ability of STAT5 activation-defective BCR/ABL SH3+SH2 mutants to induce growth factor-independent colony formation of primary mouse bone marrow progenitor cells. However, STAT5B-DAM did not rescue the growth factor-independent colony formation of kinase-deficient K1172R BCR/ABL or the triple mutant Y177F+R522L+ Y793F BCR/ABL, both of which also fail to activate STAT5. Together, these data demonstrate that STAT5 activation by BCR/ABL is dependent on signaling from more than one domain and document the important role of STAT5-regulated pathways in BCR/ABL leukemogenesis.  (+info)

Tyrosine phosphorylation of C-Cbl facilitates adhesion and spreading while suppressing anchorage-independent growth of V-Abl-transformed NIH3T3 fibroblasts. (6/343)

The protooncogenic protein c-Cbl becomes tyrosine phosphorylated in normal cells in response to a variety of external stimuli, as well as in cells transformed by oncogenic protein tyrosine kinases. Tyrosine phosphorylation of c-Cbl upregulates its binding to multiple crucial signaling molecules. However, the biological consequences of c-Cbl-mediated signaling are insufficiently understood. To analyse the biological functions of c-Cbl, we overexpressed wild-type c-Cbl and its tyrosine phosphorylation-defective mutant form in v-Abl-transformed NIH3T3 fibroblasts. In this system, wild-type c-Cbl facilitated adhesion and spreading of v-Abl-transformed fibroblasts on the extracellular matrix, while reducing anchorage independence of these cells, as measured by their colony-forming efficiency in soft agar. Therefore, overexpression of wild-type c-Cbl exhibits an overall transformation-suppressing effect. By contrast, overexpression of a tyrosine phosphorylation-defective form of c-Cbl increases neither adhesion nor anchorage dependence of v-Abl-transformed fibroblasts. Analysis of the role of individual tyrosine phosphorylation sites of c-Cbl in these phenomena indicates that both phosphatidylinositol-3' kinase and the CrkL adaptor protein may be involved in the observed effects of c-Cbl. To summarize, the results presented in this report indicate that c-Cbl is involved in regulation of cell adhesion and cytoskeletal rearrangements, and that these effects of c-Cbl are dependent on its tyrosine phosphorylation.  (+info)

Activation of the Abl tyrosine kinase in vivo by Src homology 3 domains from the Src homology 2/Src homology 3 adaptor Nck. (7/343)

The nonreceptor tyrosine kinase c-Abl is tightly regulated in vivo, but the mechanisms that normally repress its activity are not well understood. We find that a construct encoding the first two Src homology 3 (SH3) domains of the Src homology 2/SH3 adaptor protein Nck can activate c-Abl in human 293T cells. A myristoylated Nck SH3 domain construct, which is expected to localize to membranes, potently activated Abl when expressed at low levels. An unmyristoylated Nck SH3 domain construct, which localizes to the cytosol and nucleus, also activated Abl but only at high levels of expression. Activation by both myristoylated and unmyristoylated Nck constructs required the C terminus of Abl; a C-terminally truncated form of Abl was not activated, although this construct could still be activated by deletion of its SH3 domain. Activation did not require the major binding sites in the Abl C terminus for Nck SH3 domains, however, suggesting that the mechanism of activation does not require direct binding to the C terminus. Activation of c-Abl by Nck SH3 domains provides a robust experimental system for analyzing the mechanisms that normally repress Abl activity and how that normal regulation can be perturbed.  (+info)

ABL1 methylation is a distinct molecular event associated with clonal evolution of chronic myeloid leukemia. (8/343)

Methylation of the proximal promoter of the ABL1 oncogene is a common epigenetic alteration associated with clinical progression of chronic myeloid leukemia (CML). In this study we queried whether both the Ph'-associated and normal ABL1 alleles undergo methylation; what may be the proportion of hematopoietic progenitors bearing methylated ABL1 promoters in chronic versus acute phase disease; whether methylation affects the promoter uniformly or in patches with discrete clinical relevance; and, finally, whether methylation of ABL1 reflects a generalized process or is gene-specific. To address these issues, we adapted the techniques of methylation-specific PCR and bisulfite-sequencing to study the regulatory regions of ABL1 and other genes with a role in DNA repair or genotoxic stress response. In cell lines established from CML blast crisis, which only carry a single ABL1 allele nested within the BCR-ABL fusion gene, ABL1 promoters were universally methylated. By contrast, in clinical samples from patients at advanced stages of disease, both methylated and unmethylated promoter alleles were detectable. To distinguish between allele-specific methylation and a mixed cell population pattern, we studied the methylation status of ABL1 in colonies derived from single hematopoietic progenitors. Our results showed that both methylated and unmethylated promoter alleles coexisted in the same colony. Furthermore, ABL1 methylation was noted in the vast majority of colonies from blast crisis, but not chronic-phase CML. Both cell lines and clinical samples from acute-phase CML showed nearly uniform hypermethylation along the promoter region. Finally, we showed that ABL1 methylation does not reflect a generalized process and may be unique among DNA repair/genotoxic stress response genes. Our data suggest that specific methylation of the Ph'-associated ABL1 allele accompanies clonal evolution in CML.  (+info)

I'm happy to help! However, I believe there might be a slight mistake in your question. The correct term is "ABL" (Abelson murine leukemia viral oncogene homolog 1), which refers to a specific gene that encodes a tyrosine kinase protein. ABL genes can play a role in the development of certain types of cancer when they become mutated or dysregulated. Here's a brief medical definition:

ABL (Abelson murine leukemia viral oncogene homolog 1) gene:
A gene located on chromosome 9q34.1 that encodes a tyrosine kinase protein involved in various cellular processes, such as regulation of the cell cycle, differentiation, and apoptosis (programmed cell death). The ABL gene can become dysregulated or mutated, leading to the production of an abnormal tyrosine kinase protein that contributes to the development of certain types of cancer, most notably chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). The Philadelphia chromosome, a result of a reciprocal translocation between chromosomes 9 and 22, creates the abnormal fusion gene BCR-ABL, which encodes a constitutively active tyrosine kinase that drives the development of CML. Targeted therapy using tyrosine kinase inhibitors, such as imatinib (Gleevec), has been successful in treating CML and some forms of ALL with ABL mutations.

Proto-oncogene proteins c-ABL are normal cellular proteins that play crucial roles in various cellular processes, including regulation of cell growth, differentiation, and survival. They belong to the family of non-receptor tyrosine kinases and are encoded by the c-ABL gene located on chromosome 9 in humans.

The c-ABL protein is composed of several functional domains, including an N-terminal cap domain, a SRC homology 3 (SH3) domain, a SRC homology 2 (SH2) domain, and a C-terminal tyrosine kinase domain. These domains enable c-ABL to interact with other proteins and participate in signal transduction pathways that control essential cellular functions.

However, when the c-ABL gene is altered or mutated, it can become an oncogene, leading to the production of a dysregulated c-ABL protein. This abnormal protein can contribute to uncontrolled cell growth and division, ultimately resulting in cancer. One such example is the Philadelphia chromosome, a genetic alteration found in chronic myelogenous leukemia (CML) and some types of acute lymphoblastic leukemia (ALL). This abnormality arises from a reciprocal translocation between chromosomes 9 and 22, resulting in the formation of the BCR-ABL fusion gene. The resulting BCR-ABL fusion protein has constitutively active tyrosine kinase activity, leading to uncontrolled cell growth and division, which is characteristic of leukemia.

In summary, proto-oncogene proteins c-ABL are essential regulators of normal cellular processes. However, when they become dysregulated due to genetic alterations or mutations, they can contribute to the development of cancer.

A fusion protein known as "BCR-ABL" is formed due to a genetic abnormality called the Philadelphia chromosome (derived from a reciprocal translocation between chromosomes 9 and 22). This results in the formation of the oncogenic BCR-ABL tyrosine kinase, which contributes to unregulated cell growth and division, leading to chronic myeloid leukemia (CML) and some types of acute lymphoblastic leukemia (ALL). The BCR-ABL fusion protein has constitutively active tyrosine kinase activity, which results in the activation of various signaling pathways promoting cell proliferation, survival, and inhibition of apoptosis. This genetic alteration is crucial in the development and progression of CML and some types of ALL, making BCR-ABL an important therapeutic target for these malignancies.

An oncogene protein, specifically the v-abl protein, is a tyrosine kinase enzyme that plays a role in cell growth, differentiation, and survival. The v-abl gene was originally discovered in the Abelson murine leukemia virus (Ab-MLV), which is a retrovirus that can cause leukemia in mice. The viral v-abl gene is a truncated and mutated version of the cellular c-abl gene, which is normally involved in important signaling pathways within cells.

The v-abl protein has gained oncogenic potential due to its altered regulation and constitutive activation, leading to uncontrolled cell growth and division, ultimately resulting in cancer. In humans, abnormal expression or activation of the c-abl gene and its protein product have been implicated in several types of cancer, including leukemia and some solid tumors. The oncogenic nature of v-abl has made it an important target for cancer therapy, with drugs like Imatinib mesylate (Gleevec) being developed to inhibit its activity.

Chronic myelogenous leukemia (CML), BCR-ABL positive is a specific subtype of leukemia that originates in the bone marrow and involves the excessive production of mature granulocytes, a type of white blood cell. It is characterized by the presence of the Philadelphia chromosome, which is formed by a genetic translocation between chromosomes 9 and 22, resulting in the formation of the BCR-ABL fusion gene. This gene encodes for an abnormal protein with increased tyrosine kinase activity, leading to uncontrolled cell growth and division. The presence of this genetic abnormality is used to confirm the diagnosis and guide treatment decisions.

Benzamides are a class of organic compounds that consist of a benzene ring (a aromatic hydrocarbon) attached to an amide functional group. The amide group can be bound to various substituents, leading to a variety of benzamide derivatives with different biological activities.

In a medical context, some benzamides have been developed as drugs for the treatment of various conditions. For example, danzol (a benzamide derivative) is used as a hormonal therapy for endometriosis and breast cancer. Additionally, other benzamides such as sulpiride and amisulpride are used as antipsychotic medications for the treatment of schizophrenia and related disorders.

It's important to note that while some benzamides have therapeutic uses, others may be toxic or have adverse effects, so they should only be used under the supervision of a medical professional.

Pyrimidines are heterocyclic aromatic organic compounds similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring. They are one of the two types of nucleobases found in nucleic acids, the other being purines. The pyrimidine bases include cytosine (C) and thymine (T) in DNA, and uracil (U) in RNA, which pair with guanine (G) and adenine (A), respectively, through hydrogen bonding to form the double helix structure of nucleic acids. Pyrimidines are also found in many other biomolecules and have various roles in cellular metabolism and genetic regulation.

Piperazines are a class of heterocyclic organic compounds that contain a seven-membered ring with two nitrogen atoms at positions 1 and 4. They have the molecular formula N-NRR' where R and R' can be alkyl or aryl groups. Piperazines have a wide range of uses in pharmaceuticals, agrochemicals, and as building blocks in organic synthesis.

In a medical context, piperazines are used in the manufacture of various drugs, including some antipsychotics, antidepressants, antihistamines, and anti-worm medications. For example, the antipsychotic drug trifluoperazine and the antidepressant drug nefazodone both contain a piperazine ring in their chemical structure.

However, it's important to note that some piperazines are also used as recreational drugs due to their stimulant and euphoric effects. These include compounds such as BZP (benzylpiperazine) and TFMPP (trifluoromethylphenylpiperazine), which have been linked to serious health risks, including addiction, seizures, and death. Therefore, the use of these substances should be avoided.

Proto-oncogene proteins c-bcr are a group of intracellular signaling proteins that play a role in regulating cell growth, differentiation, and apoptosis (programmed cell death). They are encoded by the c-bcr gene located on chromosome 22. The c-bcr gene can fuse with the c-abl gene (located on chromosome 9) as a result of a chromosomal translocation, leading to the formation of the BCR-ABL fusion protein. This fusion protein has constitutively active tyrosine kinase activity and is associated with the development of certain types of leukemia, such as chronic myelogenous leukemia (CML).

The c-bcr gene can also fuse with other genes, leading to the formation of different fusion proteins that have been implicated in the development of other types of cancer. The normal function of c-bcr proteins is not fully understood, but they are thought to play a role in regulating the actin cytoskeleton and intracellular signaling pathways.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

K562 cells are a type of human cancer cell that are commonly used in scientific research. They are derived from a patient with chronic myelogenous leukemia (CML), a type of cancer that affects the blood and bone marrow.

K562 cells are often used as a model system to study various biological processes, including cell signaling, gene expression, differentiation, and apoptosis (programmed cell death). They are also commonly used in drug discovery and development, as they can be used to test the effectiveness of potential new therapies against cancer.

K562 cells have several characteristics that make them useful for research purposes. They are easy to grow and maintain in culture, and they can be manipulated genetically to express or knock down specific genes. Additionally, K562 cells are capable of differentiating into various cell types, such as red blood cells and megakaryocytes, which allows researchers to study the mechanisms of cell differentiation.

It's important to note that while K562 cells are a valuable tool for research, they do not fully recapitulate the complexity of human CML or other cancers. Therefore, findings from studies using K562 cells should be validated in more complex model systems or in clinical trials before they can be translated into treatments for patients.

The Philadelphia chromosome is a specific genetic alteration in certain types of leukemia and lymphoma, including chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). It is the result of a translocation between chromosomes 9 and 22, which forms an abnormal fusion gene called BCR-ABL. This gene produces an abnormal protein that leads to unregulated cell growth and division, causing cancer. The Philadelphia chromosome was first discovered in Philadelphia, USA, hence the name.

SRC homology domains, often abbreviated as SH domains, are conserved protein modules that were first identified in the SRC family of non-receptor tyrosine kinases. These domains are involved in various intracellular signaling processes and mediate protein-protein interactions. There are several types of SH domains, including:

1. SH2 domain: This domain is approximately 100 amino acids long and binds to specific phosphotyrosine-containing motifs in other proteins, thereby mediating signal transduction.
2. SH3 domain: This domain is about 60 amino acids long and recognizes proline-rich sequences in target proteins, playing a role in protein-protein interactions and intracellular signaling.
3. SH1 domain: Also known as the tyrosine kinase catalytic domain, this region contains the active site responsible for transferring a phosphate group from ATP to specific tyrosine residues on target proteins.
4. SH4 domain: This domain is present in some SRC family members and serves as a membrane-targeting module by interacting with lipids or transmembrane proteins.

These SH domains allow SRC kinases and other proteins containing them to participate in complex signaling networks that regulate various cellular processes, such as proliferation, differentiation, survival, and migration.

A blast crisis is a severe and life-threatening complication that can occur in patients with certain types of blood cancer, such as chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). It is characterized by the rapid growth and accumulation of immature blood cells, known as blasts, in the bone marrow and peripheral blood.

In a blast crisis, the blasts crowd out normal blood-forming cells in the bone marrow, leading to a significant decrease in the production of healthy red blood cells, white blood cells, and platelets. This can result in symptoms such as anemia, fatigue, infection, easy bruising or bleeding, and an enlarged spleen.

Blast crisis is often treated with aggressive chemotherapy, targeted therapy, or stem cell transplantation to eliminate the abnormal blasts and restore normal blood cell production. The prognosis for patients in blast crisis can be poor, depending on the type of leukemia, the patient's age and overall health, and the response to treatment.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Proto-oncogene proteins, such as the c-Crk protein, are normal cellular proteins that play crucial roles in various cellular processes including regulation of cell growth, division, and survival. When proto-oncogenes are mutated or functionally altered, they can become oncogenes, promoting uncontrolled cell growth and leading to cancer.

The c-Crk protein is a non-receptor tyrosine kinase adapter protein that plays a significant role in signal transduction pathways, particularly those involved in cell adhesion, migration, differentiation, and oncogenic transformation. It has two main isoforms, CrkI and CrkII, which differ in their structural organization but share a similar functional domain structure. These domains include an N-terminal Src homology 3 (SH3) domain, a central SH2 domain, and a C-terminal SH3 domain.

The SH3 domains of c-Crk proteins are responsible for binding to various partner proteins containing proline-rich motifs, while the SH2 domain binds to phosphorylated tyrosine residues on target proteins. Through these interactions, c-Crk proteins facilitate the formation of multi-protein complexes and help transmit signals from activated receptor tyrosine kinases (RTKs) or non-receptor tyrosine kinases (NRTKs) to downstream effectors.

Dysregulation of c-Crk proteins, through genetic alterations or aberrant signaling, can contribute to oncogenic transformation and tumor progression. For example, increased c-Crk expression or activation has been implicated in several types of cancer, including leukemias, lymphomas, and solid tumors.

Chronic myeloid leukemia (CML), atypical, BCR-ABL negative is a rare subtype of CML that does not have the typical Philadelphia chromosome abnormality or the resulting BCR-ABL fusion gene. This means that the disease lacks the constitutively active tyrosine kinase that is targeted by imatinib mesylate (Gleevec) and other similar drugs.

The atypical form of CML is often characterized by a more aggressive clinical course, with a higher risk of transformation to acute leukemia compared to the classic form of CML. It can be difficult to diagnose and treat due to its rarity and heterogeneity. Treatment options may include chemotherapy, targeted therapy, stem cell transplantation, or a combination of these approaches. Regular follow-up with blood tests and bone marrow examinations is essential for monitoring the disease course and adjusting treatment as necessary.

Human chromosome pair 9 consists of two rod-shaped structures present in the nucleus of each cell of the human body. Each member of the pair contains thousands of genes and other genetic material, encoded in the form of DNA molecules. The two chromosomes in a pair are identical or very similar to each other in terms of their size, shape, and genetic makeup.

Chromosome 9 is one of the autosomal chromosomes, meaning that it is not a sex chromosome (X or Y) and is present in two copies in all cells of the body, regardless of sex. Chromosome 9 is a medium-sized chromosome, and it is estimated to contain around 135 million base pairs of DNA and approximately 1200 genes.

Chromosome 9 contains several important genes that are associated with various human traits and diseases. For example, mutations in the gene that encodes the protein APOE on chromosome 9 have been linked to an increased risk of developing Alzheimer's disease. Additionally, variations in the gene that encodes the protein EGFR on chromosome 9 have been associated with an increased risk of developing certain types of cancer.

Overall, human chromosome pair 9 plays a critical role in the development and function of the human body, and variations in its genetic makeup can contribute to a wide range of traits and diseases.

Abetalipoproteinemia is a rare inherited genetic disorder that affects the way the body absorbs and metabolizes fats and fat-soluble vitamins. It is caused by mutations in the genes responsible for producing proteins involved in the formation and transport of beta-lipoproteins, which are necessary for the absorption of dietary fats and cholesterol from the intestines.

Individuals with abetalipoproteinemia are unable to produce adequate levels of these lipoproteins, leading to a deficiency in fat-soluble vitamins (A, D, E, and K) and an accumulation of fats in the intestines. This results in various symptoms such as steatorrhea (fatty, foul-smelling stools), malabsorption, diarrhea, failure to thrive, and neurological issues due to vitamin E deficiency.

The disorder is typically diagnosed in infancy or early childhood and requires lifelong dietary management, including a low-fat diet and supplementation with fat-soluble vitamins. Early intervention can help prevent the progression of neurological symptoms and improve overall prognosis.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Neoplastic cell transformation is a process in which a normal cell undergoes genetic alterations that cause it to become cancerous or malignant. This process involves changes in the cell's DNA that result in uncontrolled cell growth and division, loss of contact inhibition, and the ability to invade surrounding tissues and metastasize (spread) to other parts of the body.

Neoplastic transformation can occur as a result of various factors, including genetic mutations, exposure to carcinogens, viral infections, chronic inflammation, and aging. These changes can lead to the activation of oncogenes or the inactivation of tumor suppressor genes, which regulate cell growth and division.

The transformation of normal cells into cancerous cells is a complex and multi-step process that involves multiple genetic and epigenetic alterations. It is characterized by several hallmarks, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabling replicative immortality, induction of angiogenesis, activation of invasion and metastasis, reprogramming of energy metabolism, and evading immune destruction.

Neoplastic cell transformation is a fundamental concept in cancer biology and is critical for understanding the molecular mechanisms underlying cancer development and progression. It also has important implications for cancer diagnosis, prognosis, and treatment, as identifying the specific genetic alterations that underlie neoplastic transformation can help guide targeted therapies and personalized medicine approaches.

Human chromosome pair 22 consists of two rod-shaped structures present in the nucleus of each cell in the human body. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex structure called a chromatin.

Chromosome pair 22 is one of the 22 autosomal pairs of human chromosomes, meaning they are not sex chromosomes (X or Y). Chromosome 22 is the second smallest human chromosome, with each arm of the chromosome designated as p and q. The short arm is labeled "p," and the long arm is labeled "q."

Chromosome 22 contains several genes that are associated with various genetic disorders, including DiGeorge syndrome, velocardiofacial syndrome, and cat-eye syndrome, which result from deletions or duplications of specific regions on the chromosome. Additionally, chromosome 22 is the location of the NRXN1 gene, which has been associated with an increased risk for autism spectrum disorder (ASD) and schizophrenia when deleted or disrupted.

Understanding the genetic makeup of human chromosome pair 22 can provide valuable insights into human genetics, evolution, and disease susceptibility, as well as inform medical diagnoses, treatments, and research.

Drug resistance in neoplasms (also known as cancer drug resistance) refers to the ability of cancer cells to withstand the effects of chemotherapeutic agents or medications designed to kill or inhibit the growth of cancer cells. This can occur due to various mechanisms, including changes in the cancer cell's genetic makeup, alterations in drug targets, increased activity of drug efflux pumps, and activation of survival pathways.

Drug resistance can be intrinsic (present at the beginning of treatment) or acquired (developed during the course of treatment). It is a significant challenge in cancer therapy as it often leads to reduced treatment effectiveness, disease progression, and poor patient outcomes. Strategies to overcome drug resistance include the use of combination therapies, development of new drugs that target different mechanisms, and personalized medicine approaches that consider individual patient and tumor characteristics.

Gene expression regulation in leukemia refers to the processes that control the production or activation of specific proteins encoded by genes in leukemic cells. These regulatory mechanisms include various molecular interactions that can either promote or inhibit gene transcription and translation. In leukemia, abnormal gene expression regulation can lead to uncontrolled proliferation, differentiation arrest, and accumulation of malignant white blood cells (leukemia cells) in the bone marrow and peripheral blood.

Dysregulated gene expression in leukemia may involve genetic alterations such as mutations, chromosomal translocations, or epigenetic changes that affect DNA methylation patterns and histone modifications. These changes can result in the overexpression of oncogenes (genes with cancer-promoting functions) or underexpression of tumor suppressor genes (genes that prevent uncontrolled cell growth).

Understanding gene expression regulation in leukemia is crucial for developing targeted therapies and improving diagnostic, prognostic, and treatment strategies.

Translocation, genetic, refers to a type of chromosomal abnormality in which a segment of a chromosome is transferred from one chromosome to another, resulting in an altered genome. This can occur between two non-homologous chromosomes (non-reciprocal translocation) or between two homologous chromosomes (reciprocal translocation). Genetic translocations can lead to various clinical consequences, depending on the genes involved and the location of the translocation. Some translocations may result in no apparent effects, while others can cause developmental abnormalities, cancer, or other genetic disorders. In some cases, translocations can also increase the risk of having offspring with genetic conditions.

The Abelson murine leukemia virus (Abelson murine leukemia virus, or A-MuLV) is a type of retrovirus that can cause cancer in mice. It was first discovered in 1970 and has since been widely studied as a model system for understanding the mechanisms of retroviral infection and cancer development.

A-MuLV is named after Peter Nowell and David A. Harrison, who first described the virus and its ability to cause leukemia in mice. The virus contains an oncogene called "v-abl," which encodes a tyrosine kinase enzyme that can activate various signaling pathways involved in cell growth and division. When the v-abl oncogene is integrated into the genome of an infected mouse cell, it can cause uncontrolled cell growth and division, leading to the development of leukemia.

A-MuLV has been used extensively in laboratory research to study the molecular mechanisms of cancer development and to develop new therapies for treating cancer. It has also been used as a tool for introducing specific genetic modifications into mouse cells, allowing researchers to study the effects of those modifications on cell behavior and function.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Tyrosine is an non-essential amino acid, which means that it can be synthesized by the human body from another amino acid called phenylalanine. Its name is derived from the Greek word "tyros," which means cheese, as it was first isolated from casein, a protein found in cheese.

Tyrosine plays a crucial role in the production of several important substances in the body, including neurotransmitters such as dopamine, norepinephrine, and epinephrine, which are involved in various physiological processes, including mood regulation, stress response, and cognitive functions. It also serves as a precursor to melanin, the pigment responsible for skin, hair, and eye color.

In addition, tyrosine is involved in the structure of proteins and is essential for normal growth and development. Some individuals may require tyrosine supplementation if they have a genetic disorder that affects tyrosine metabolism or if they are phenylketonurics (PKU), who cannot metabolize phenylalanine, which can lead to elevated tyrosine levels in the blood. However, it is important to consult with a healthcare professional before starting any supplementation regimen.

Oncogene proteins are derived from oncogenes, which are genes that have the potential to cause cancer. Normally, these genes help regulate cell growth and division, but when they become altered or mutated, they can become overactive and lead to uncontrolled cell growth and division, which is a hallmark of cancer. Oncogene proteins can contribute to tumor formation and progression by promoting processes such as cell proliferation, survival, angiogenesis, and metastasis. Examples of oncogene proteins include HER2/neu, EGFR, and BCR-ABL.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.

Thiazoles are organic compounds that contain a heterocyclic ring consisting of a nitrogen atom and a sulfur atom, along with two carbon atoms and two hydrogen atoms. They have the chemical formula C3H4NS. Thiazoles are present in various natural and synthetic substances, including some vitamins, drugs, and dyes. In the context of medicine, thiazole derivatives have been developed as pharmaceuticals for their diverse biological activities, such as anti-inflammatory, antifungal, antibacterial, and antihypertensive properties. Some well-known examples include thiazide diuretics (e.g., hydrochlorothiazide) used to treat high blood pressure and edema, and the antidiabetic drug pioglitazone.

Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.

When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.

Examples of proto-oncogene proteins include:

1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.

Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Adaptor proteins are a type of protein that play a crucial role in intracellular signaling pathways by serving as a link between different components of the signaling complex. Specifically, "signal transducing adaptor proteins" refer to those adaptor proteins that are involved in signal transduction processes, where they help to transmit signals from the cell surface receptors to various intracellular effectors. These proteins typically contain modular domains that allow them to interact with multiple partners, thereby facilitating the formation of large signaling complexes and enabling the integration of signals from different pathways.

Signal transducing adaptor proteins can be classified into several families based on their structural features, including the Src homology 2 (SH2) domain, the Src homology 3 (SH3) domain, and the phosphotyrosine-binding (PTB) domain. These domains enable the adaptor proteins to recognize and bind to specific motifs on other signaling molecules, such as receptor tyrosine kinases, G protein-coupled receptors, and cytokine receptors.

One well-known example of a signal transducing adaptor protein is the growth factor receptor-bound protein 2 (Grb2), which contains an SH2 domain that binds to phosphotyrosine residues on activated receptor tyrosine kinases. Grb2 also contains an SH3 domain that interacts with proline-rich motifs on other signaling proteins, such as the guanine nucleotide exchange factor SOS. This interaction facilitates the activation of the Ras small GTPase and downstream signaling pathways involved in cell growth, differentiation, and survival.

Overall, signal transducing adaptor proteins play a critical role in regulating various cellular processes by modulating intracellular signaling pathways in response to extracellular stimuli. Dysregulation of these proteins has been implicated in various diseases, including cancer and inflammatory disorders.

Oncogenes are genes that have the potential to cause cancer. They can do this by promoting cell growth and division (cellular proliferation), preventing cell death (apoptosis), or enabling cells to invade surrounding tissue and spread to other parts of the body (metastasis). Oncogenes can be formed when normal genes, called proto-oncogenes, are mutated or altered in some way. This can happen as a result of exposure to certain chemicals or radiation, or through inherited genetic mutations. When activated, oncogenes can contribute to the development of cancer by causing cells to divide and grow in an uncontrolled manner.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Phosphotyrosine is not a medical term per se, but rather a biochemical term used in the field of medicine and life sciences.

Phosphotyrosine is a post-translational modification of tyrosine residues in proteins, where a phosphate group is added to the hydroxyl side chain of tyrosine by protein kinases. This modification plays a crucial role in intracellular signaling pathways and regulates various cellular processes such as cell growth, differentiation, and apoptosis. Abnormalities in phosphotyrosine-mediated signaling have been implicated in several diseases, including cancer and diabetes.

Experimental leukemia refers to the stage of research or clinical trials where new therapies, treatments, or diagnostic methods are being studied for leukemia. Leukemia is a type of cancer that affects the blood and bone marrow, leading to an overproduction of abnormal white blood cells.

In the experimental stage, researchers investigate various aspects of leukemia, such as its causes, progression, and potential treatments. They may conduct laboratory studies using cell cultures or animal models to understand the disease better and test new therapeutic approaches. Additionally, clinical trials may be conducted to evaluate the safety and efficacy of novel treatments in human patients with leukemia.

Experimental research in leukemia is crucial for advancing our understanding of the disease and developing more effective treatment strategies. It involves a rigorous and systematic process that adheres to ethical guidelines and scientific standards to ensure the validity and reliability of the findings.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Precursor Cell Lymphoblastic Leukemia-Lymphoma (previously known as Precursor T-lymphoblastic Leukemia/Lymphoma) is a type of cancer that affects the early stages of T-cell development. It is a subtype of acute lymphoblastic leukemia (ALL), which is characterized by the overproduction of immature white blood cells called lymphoblasts in the bone marrow, blood, and other organs.

In Precursor Cell Lymphoblastic Leukemia-Lymphoma, these abnormal lymphoblasts accumulate primarily in the lymphoid tissues such as the thymus and lymph nodes, leading to the enlargement of these organs. This subtype is more aggressive than other forms of ALL and has a higher risk of spreading to the central nervous system (CNS).

The medical definition of Precursor Cell Lymphoblastic Leukemia-Lymphoma includes:

1. A malignant neoplasm of immature T-cell precursors, also known as lymphoblasts.
2. Characterized by the proliferation and accumulation of these abnormal cells in the bone marrow, blood, and lymphoid tissues such as the thymus and lymph nodes.
3. Often associated with chromosomal abnormalities, genetic mutations, or aberrant gene expression that contribute to its aggressive behavior and poor prognosis.
4. Typically presents with symptoms related to bone marrow failure (anemia, neutropenia, thrombocytopenia), lymphadenopathy (swollen lymph nodes), hepatosplenomegaly (enlarged liver and spleen), and potential CNS involvement.
5. Diagnosed through a combination of clinical evaluation, imaging studies, and laboratory tests, including bone marrow aspiration and biopsy, immunophenotyping, cytogenetic analysis, and molecular genetic testing.
6. Treated with intensive multi-agent chemotherapy regimens, often combined with radiation therapy and/or stem cell transplantation to achieve remission and improve survival outcomes.

An oncogene protein fusion is a result of a genetic alteration in which parts of two different genes combine to create a hybrid gene that can contribute to the development of cancer. This fusion can lead to the production of an abnormal protein that promotes uncontrolled cell growth and division, ultimately resulting in a malignant tumor. Oncogene protein fusions are often caused by chromosomal rearrangements such as translocations, inversions, or deletions and are commonly found in various types of cancer, including leukemia and sarcoma. These genetic alterations can serve as potential targets for cancer diagnosis and therapy.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Recombinant fusion proteins are artificially created biomolecules that combine the functional domains or properties of two or more different proteins into a single protein entity. They are generated through recombinant DNA technology, where the genes encoding the desired protein domains are linked together and expressed as a single, chimeric gene in a host organism, such as bacteria, yeast, or mammalian cells.

The resulting fusion protein retains the functional properties of its individual constituent proteins, allowing for novel applications in research, diagnostics, and therapeutics. For instance, recombinant fusion proteins can be designed to enhance protein stability, solubility, or immunogenicity, making them valuable tools for studying protein-protein interactions, developing targeted therapies, or generating vaccines against infectious diseases or cancer.

Examples of recombinant fusion proteins include:

1. Etaglunatide (ABT-523): A soluble Fc fusion protein that combines the heavy chain fragment crystallizable region (Fc) of an immunoglobulin with the extracellular domain of the human interleukin-6 receptor (IL-6R). This fusion protein functions as a decoy receptor, neutralizing IL-6 and its downstream signaling pathways in rheumatoid arthritis.
2. Etanercept (Enbrel): A soluble TNF receptor p75 Fc fusion protein that binds to tumor necrosis factor-alpha (TNF-α) and inhibits its proinflammatory activity, making it a valuable therapeutic option for treating autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, and psoriasis.
3. Abatacept (Orencia): A fusion protein consisting of the extracellular domain of cytotoxic T-lymphocyte antigen 4 (CTLA-4) linked to the Fc region of an immunoglobulin, which downregulates T-cell activation and proliferation in autoimmune diseases like rheumatoid arthritis.
4. Belimumab (Benlysta): A monoclonal antibody that targets B-lymphocyte stimulator (BLyS) protein, preventing its interaction with the B-cell surface receptor and inhibiting B-cell activation in systemic lupus erythematosus (SLE).
5. Romiplostim (Nplate): A fusion protein consisting of a thrombopoietin receptor agonist peptide linked to an immunoglobulin Fc region, which stimulates platelet production in patients with chronic immune thrombocytopenia (ITP).
6. Darbepoetin alfa (Aranesp): A hyperglycosylated erythropoiesis-stimulating protein that functions as a longer-acting form of recombinant human erythropoietin, used to treat anemia in patients with chronic kidney disease or cancer.
7. Palivizumab (Synagis): A monoclonal antibody directed against the F protein of respiratory syncytial virus (RSV), which prevents RSV infection and is administered prophylactically to high-risk infants during the RSV season.
8. Ranibizumab (Lucentis): A recombinant humanized monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor A (VEGF-A), used in the treatment of age-related macular degeneration, diabetic retinopathy, and other ocular disorders.
9. Cetuximab (Erbitux): A chimeric monoclonal antibody that binds to epidermal growth factor receptor (EGFR), used in the treatment of colorectal cancer and head and neck squamous cell carcinoma.
10. Adalimumab (Humira): A fully humanized monoclonal antibody that targets tumor necrosis factor-alpha (TNF-α), used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriasis, and Crohn's disease.
11. Bevacizumab (Avastin): A recombinant humanized monoclonal antibody that binds to VEGF-A, used in the treatment of various cancers, including colorectal, lung, breast, and kidney cancer.
12. Trastuzumab (Herceptin): A humanized monoclonal antibody that targets HER2/neu receptor, used in the treatment of breast cancer.
13. Rituximab (Rituxan): A chimeric monoclonal antibody that binds to CD20 antigen on B cells, used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis.
14. Palivizumab (Synagis): A humanized monoclonal antibody that binds to the F protein of respiratory syncytial virus, used in the prevention of respiratory syncytial virus infection in high-risk infants.
15. Infliximab (Remicade): A chimeric monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.
16. Natalizumab (Tysabri): A humanized monoclonal antibody that binds to α4β1 integrin, used in the treatment of multiple sclerosis and Crohn's disease.
17. Adalimumab (Humira): A fully human monoclonal antibody that targets TNF-α, used in the treatment of various inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis.
18. Golimumab (Simponi): A fully human monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.
19. Certolizumab pegol (Cimzia): A PEGylated Fab' fragment of a humanized monoclonal antibody that targets TNF-α, used in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.
20. Ustekinumab (Stelara): A fully human monoclonal antibody that targets IL-12 and IL-23, used in the treatment of psoriasis, psoriatic arthritis, and Crohn's disease.
21. Secukinumab (Cosentyx): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis.
22. Ixekizumab (Taltz): A fully human monoclonal antibody that targets IL-17A, used in the treatment of psoriasis and psoriatic arthritis.
23. Brodalumab (Siliq): A fully human monoclonal antibody that targets IL-17 receptor A, used in the treatment of psoriasis.
24. Sarilumab (Kevzara): A fully human monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis.
25. Tocilizumab (Actemra): A humanized monoclonal antibody that targets the IL-6 receptor, used in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, and chimeric antigen receptor T-cell-induced cytokine release syndrome.
26. Siltuximab (Sylvant): A chimeric monoclonal antibody that targets IL-6, used in the treatment of multicentric Castleman disease.
27. Satralizumab (Enspryng): A humanized monoclonal antibody that targets IL-6 receptor alpha, used in the treatment of neuromyelitis optica spectrum disorder.
28. Sirukumab (Plivensia): A human monoclonal antibody that targets IL-6, used in the treatment

A "cell line, transformed" is a type of cell culture that has undergone a stable genetic alteration, which confers the ability to grow indefinitely in vitro, outside of the organism from which it was derived. These cells have typically been immortalized through exposure to chemical or viral carcinogens, or by introducing specific oncogenes that disrupt normal cell growth regulation pathways.

Transformed cell lines are widely used in scientific research because they offer a consistent and renewable source of biological material for experimentation. They can be used to study various aspects of cell biology, including signal transduction, gene expression, drug discovery, and toxicity testing. However, it is important to note that transformed cells may not always behave identically to their normal counterparts, and results obtained using these cells should be validated in more physiologically relevant systems when possible.

Myeloproliferative disorders (MPDs) are a group of rare, chronic blood cancers that originate from the abnormal proliferation or growth of one or more types of blood-forming cells in the bone marrow. These disorders result in an overproduction of mature but dysfunctional blood cells, which can lead to serious complications such as blood clots, bleeding, and organ damage.

There are several subtypes of MPDs, including:

1. Chronic Myeloid Leukemia (CML): A disorder characterized by the overproduction of mature granulocytes (a type of white blood cell) in the bone marrow, leading to an increased number of these cells in the blood. CML is caused by a genetic mutation that results in the formation of the BCR-ABL fusion protein, which drives uncontrolled cell growth and division.
2. Polycythemia Vera (PV): A disorder characterized by the overproduction of all three types of blood cells - red blood cells, white blood cells, and platelets - in the bone marrow. This can lead to an increased risk of blood clots, bleeding, and enlargement of the spleen.
3. Essential Thrombocythemia (ET): A disorder characterized by the overproduction of platelets in the bone marrow, leading to an increased risk of blood clots and bleeding.
4. Primary Myelofibrosis (PMF): A disorder characterized by the replacement of normal bone marrow tissue with scar tissue, leading to impaired blood cell production and anemia, enlargement of the spleen, and increased risk of infections and bleeding.
5. Chronic Neutrophilic Leukemia (CNL): A rare disorder characterized by the overproduction of neutrophils (a type of white blood cell) in the bone marrow, leading to an increased number of these cells in the blood. CNL can lead to an increased risk of infections and organ damage.

MPDs are typically treated with a combination of therapies, including chemotherapy, targeted therapy, immunotherapy, and stem cell transplantation. The choice of treatment depends on several factors, including the subtype of MPD, the patient's age and overall health, and the presence of any comorbidities.

Stat5 (Signal Transducer and Activator of Transcription 5) is a transcription factor that plays a crucial role in various cellular processes, including growth, survival, and differentiation. It exists in two closely related isoforms, Stat5a and Stat5b, which are encoded by separate genes but share significant sequence homology and functional similarity.

When activated through phosphorylation by receptor or non-receptor tyrosine kinases, Stat5 forms homodimers or heterodimers that translocate to the nucleus. Once in the nucleus, these dimers bind to specific DNA sequences called Stat-binding elements (SBEs) in the promoter regions of target genes, leading to their transcriptional activation or repression.

Stat5 is involved in various physiological and pathological conditions, such as hematopoiesis, lactation, immune response, and cancer progression. Dysregulation of Stat5 signaling has been implicated in several malignancies, including leukemias, lymphomas, and breast cancer, making it an attractive therapeutic target for these diseases.

Leukemia is a type of cancer that originates from the bone marrow - the soft, inner part of certain bones where new blood cells are made. It is characterized by an abnormal production of white blood cells, known as leukocytes or blasts. These abnormal cells accumulate in the bone marrow and interfere with the production of normal blood cells, leading to a decrease in red blood cells (anemia), platelets (thrombocytopenia), and healthy white blood cells (leukopenia).

There are several types of leukemia, classified based on the specific type of white blood cell affected and the speed at which the disease progresses:

1. Acute Leukemias - These types of leukemia progress rapidly, with symptoms developing over a few weeks or months. They involve the rapid growth and accumulation of immature, nonfunctional white blood cells (blasts) in the bone marrow and peripheral blood. The two main categories are:
- Acute Lymphoblastic Leukemia (ALL) - Originates from lymphoid progenitor cells, primarily affecting children but can also occur in adults.
- Acute Myeloid Leukemia (AML) - Develops from myeloid progenitor cells and is more common in older adults.

2. Chronic Leukemias - These types of leukemia progress slowly, with symptoms developing over a period of months to years. They involve the production of relatively mature, but still abnormal, white blood cells that can accumulate in large numbers in the bone marrow and peripheral blood. The two main categories are:
- Chronic Lymphocytic Leukemia (CLL) - Affects B-lymphocytes and is more common in older adults.
- Chronic Myeloid Leukemia (CML) - Originates from myeloid progenitor cells, characterized by the presence of a specific genetic abnormality called the Philadelphia chromosome. It can occur at any age but is more common in middle-aged and older adults.

Treatment options for leukemia depend on the type, stage, and individual patient factors. Treatments may include chemotherapy, targeted therapy, immunotherapy, stem cell transplantation, or a combination of these approaches.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

Milk proteins are a complex mixture of proteins that are naturally present in milk, consisting of casein and whey proteins. Casein makes up about 80% of the total milk protein and is divided into several types including alpha-, beta-, gamma- and kappa-casein. Whey proteins account for the remaining 20% and include beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin, and immunoglobulins. These proteins are important sources of essential amino acids and play a crucial role in the nutrition of infants and young children. Additionally, milk proteins have various functional properties that are widely used in the food industry for their gelling, emulsifying, and foaming abilities.

Interleukin-3 (IL-3) is a type of cytokine, which is a small signaling protein that modulates the immune response, cell growth, and differentiation. IL-3 is primarily produced by activated T cells and mast cells. It plays an essential role in the survival, proliferation, and differentiation of hematopoietic stem cells, which give rise to all blood cell types. Specifically, IL-3 supports the development of myeloid lineage cells, including basophils, eosinophils, mast cells, megakaryocytes, and erythroid progenitors.

IL-3 binds to its receptor, the interleukin-3 receptor (IL-3R), which consists of two subunits: CD123 (the alpha chain) and CD131 (the beta chain). The binding of IL-3 to its receptor triggers a signaling cascade within the cell that ultimately leads to changes in gene expression, promoting cell growth and differentiation. Dysregulation of IL-3 production or signaling has been implicated in several hematological disorders, such as leukemia and myelodysplastic syndromes.

Chronic myeloid leukemia (CML) is a type of cancer that starts in certain blood-forming cells of the bone marrow. In chronic phase CML, the disease progresses slowly and may not cause any symptoms for a period of time. It is characterized by the overproduction of mature and immature white blood cells, called myeloid cells. These cells accumulate in the bone marrow and interfere with the production of normal blood cells, leading to anemia, fatigue, easy bruising, and increased risk of infection. The distinguishing genetic feature of CML is the presence of the Philadelphia chromosome, which is formed by a genetic translocation between chromosomes 9 and 22, resulting in the formation of the BCR-ABL fusion gene. This gene produces an abnormal protein that contributes to the development of leukemia. The chronic phase of CML can last for several years and is typically treated with targeted therapy such as tyrosine kinase inhibitors (TKIs) which target the BCR-ABL protein.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

RNA (Ribonucleic acid) is a single-stranded molecule similar in structure to DNA, involved in the process of protein synthesis in the cell. It acts as a messenger carrying genetic information from DNA to the ribosomes, where proteins are produced.

A neoplasm, on the other hand, is an abnormal growth of cells, which can be benign or malignant. Benign neoplasms are not cancerous and do not invade nearby tissues or spread to other parts of the body. Malignant neoplasms, however, are cancerous and have the potential to invade surrounding tissues and spread to distant sites in the body through a process called metastasis.

Therefore, an 'RNA neoplasm' is not a recognized medical term as RNA is not a type of growth or tumor. However, there are certain types of cancer-causing viruses known as oncoviruses that contain RNA as their genetic material and can cause neoplasms. For example, human T-cell leukemia virus (HTLV-1) and hepatitis C virus (HCV) are RNA viruses that can cause certain types of cancer in humans.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

Leukemia, myeloid is a type of cancer that originates in the bone marrow, where blood cells are produced. Myeloid leukemia affects the myeloid cells, which include red blood cells, platelets, and most types of white blood cells. In this condition, the bone marrow produces abnormal myeloid cells that do not mature properly and accumulate in the bone marrow and blood. These abnormal cells hinder the production of normal blood cells, leading to various symptoms such as anemia, fatigue, increased risk of infections, and easy bruising or bleeding.

There are several types of myeloid leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). AML progresses rapidly and requires immediate treatment, while CML tends to progress more slowly. The exact causes of myeloid leukemia are not fully understood, but risk factors include exposure to radiation or certain chemicals, smoking, genetic disorders, and a history of chemotherapy or other cancer treatments.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

The Wiskott-Aldrich Syndrome Protein (WASP) family is a group of proteins that play crucial roles in actin cytoskeleton regulation, which is essential for various cellular processes such as cell motility, membrane trafficking, and immune synapse formation. The family includes WASP, N-WASP (Neural WASP), WAVE1 (WASP-family verprolin homologous protein 1), WAVE2, WAVE3, and WHAMM (WASP Homology Associated with Actin, Membranes and Microtubules). These proteins share a common structural feature called the WASP homology domain 2 (WH2) that binds to actin monomers, and a C-terminal verprolin homology domain (VHD) that interacts with various regulatory factors. Mutations in the gene encoding WASP can lead to Wiskott-Aldrich syndrome, an X-linked recessive disorder characterized by microthrombocytopenia, eczema, and recurrent infections.

In situ hybridization, fluorescence (FISH) is a type of molecular cytogenetic technique used to detect and localize the presence or absence of specific DNA sequences on chromosomes through the use of fluorescent probes. This technique allows for the direct visualization of genetic material at a cellular level, making it possible to identify chromosomal abnormalities such as deletions, duplications, translocations, and other rearrangements.

The process involves denaturing the DNA in the sample to separate the double-stranded molecules into single strands, then adding fluorescently labeled probes that are complementary to the target DNA sequence. The probe hybridizes to the complementary sequence in the sample, and the location of the probe is detected by fluorescence microscopy.

FISH has a wide range of applications in both clinical and research settings, including prenatal diagnosis, cancer diagnosis and monitoring, and the study of gene expression and regulation. It is a powerful tool for identifying genetic abnormalities and understanding their role in human disease.

v-Cbl is a type of oncogene protein that is derived from the cellular c-Cbl protein. Oncogenes are genes that have the potential to cause cancer, and they can do this by promoting cell growth and division when they should not. The v-Cbl protein is created when a virus called the avian reticuloendotheliosis virus infects a host cell and inserts its own version of the c-Cbl gene into the host's DNA. This results in the production of the abnormal v-Cbl protein, which can contribute to the development of cancer by disrupting the normal regulation of cell growth and division.

The c-Cbl protein is a type of E3 ubiquitin ligase, which is an enzyme that helps to tag other proteins for degradation. The v-Cbl protein retains this function, but it also has additional activities that allow it to promote cell growth and division. For example, v-Cbl can activate signaling pathways that lead to the activation of transcription factors, which are proteins that control the expression of genes involved in cell growth and division.

In addition to its role in cancer, v-Cbl has also been implicated in the development of other diseases, including immune disorders and neurological conditions. However, more research is needed to fully understand the various functions of this oncogene protein and how it contributes to disease.

Proto-oncogene proteins, like c-Pim-1, are normal cellular proteins that play crucial roles in various cellular processes such as cell growth, differentiation, and survival. When these genes undergo mutations or are overexpressed, they can become oncogenes, which contribute to the development of cancer.

The c-Pim-1 protein is a serine/threonine kinase that regulates various signaling pathways involved in cell proliferation, survival, and migration. It is encoded by the PIM1 gene located on human chromosome 6. In normal cells, c-Pim-1 expression is tightly regulated and plays a role in hematopoietic stem cell maintenance and T-cell development.

However, deregulation of c-Pim-1 has been implicated in several types of cancer, including leukemia, lymphoma, and solid tumors. Overexpression of c-Pim-1 can lead to uncontrolled cell growth, resistance to apoptosis, and increased cell migration, promoting tumor progression and metastasis. Inhibition of c-Pim-1 kinase activity has been explored as a potential therapeutic strategy in cancer treatment.

Actin is a type of protein that forms part of the contractile apparatus in muscle cells, and is also found in various other cell types. It is a globular protein that polymerizes to form long filaments, which are important for many cellular processes such as cell division, cell motility, and the maintenance of cell shape. In muscle cells, actin filaments interact with another type of protein called myosin to enable muscle contraction. Actins can be further divided into different subtypes, including alpha-actin, beta-actin, and gamma-actin, which have distinct functions and expression patterns in the body.

Proto-oncogene proteins c-cbl are a group of E3 ubiquitin ligases that play crucial roles in regulating various cellular processes, including cell survival, proliferation, differentiation, and migration. The c-cbl gene encodes for the c-Cbl protein, which is a member of the Cbl family of proteins that also includes Cbl-b and Cbl-c.

The c-Cbl protein contains several functional domains, including an N-terminal tyrosine kinase binding domain, a RING finger domain, a proline-rich region, and a C-terminal ubiquitin association domain. These domains enable c-Cbl to interact with various signaling molecules, such as receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and growth factor receptors, and regulate their activity through ubiquitination.

Ubiquitination is a post-translational modification that involves the addition of ubiquitin molecules to proteins, leading to their degradation or altered function. c-Cbl functions as an E3 ubiquitin ligase, which catalyzes the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a specific target protein.

Proto-oncogene proteins c-cbl can act as tumor suppressors by negatively regulating signaling pathways that promote cell growth and survival. Mutations in the c-cbl gene or dysregulation of c-Cbl function have been implicated in various types of cancer, including leukemia, lymphoma, and solid tumors. These mutations can lead to increased RTK signaling, enhanced cell proliferation, and decreased apoptosis, contributing to tumor development and progression.

Tertiary protein structure refers to the three-dimensional arrangement of all the elements (polypeptide chains) of a single protein molecule. It is the highest level of structural organization and results from interactions between various side chains (R groups) of the amino acids that make up the protein. These interactions, which include hydrogen bonds, ionic bonds, van der Waals forces, and disulfide bridges, give the protein its unique shape and stability, which in turn determines its function. The tertiary structure of a protein can be stabilized by various factors such as temperature, pH, and the presence of certain ions. Any changes in these factors can lead to denaturation, where the protein loses its tertiary structure and thus its function.

Receptor-like protein tyrosine phosphatases (RPTPs) are a subclass of protein tyrosine phosphatases that possess an extracellular domain, a transmembrane domain, and an intracellular domain with tyrosine phosphatase activity. They play crucial roles in various cellular processes, including cell growth, differentiation, migration, and survival, by regulating the balance of protein tyrosine phosphorylation. RPTPs can act as receptors, interacting with extracellular ligands to initiate intracellular signaling cascades. Dysregulation of RPTPs has been implicated in several human diseases, including cancer and neurological disorders.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Crk-associated substrate protein, often abbreviated as CAS or CAS-L (for Crk-associated substrate lymphocyte type), is a signaling adaptor protein that plays a role in various cellular processes such as proliferation, differentiation, and survival. It is called a "substrate" because it can be phosphorylated by various kinases and serves as a platform for the assembly of signaling complexes.

CAS contains several domains that allow it to interact with other proteins, including Src homology 3 (SH3) domains, which bind to proline-rich sequences in partner proteins, and a SH2 domain, which binds to phosphorylated tyrosine residues. These interactions enable CAS to link upstream signaling events with downstream effectors, thereby regulating various cellular responses.

CAS is often found downstream of receptor tyrosine kinases (RTKs) and integrins, and has been implicated in the regulation of several signaling pathways, including the Ras/MAPK, PI3K/Akt, and JNK pathways. Mutations or dysregulation of CAS have been associated with various diseases, including cancer and neurological disorders.

Retroviridae is a family of viruses that includes human immunodeficiency virus (HIV) and other viruses that primarily use RNA as their genetic material. The name "retrovirus" comes from the fact that these viruses reverse transcribe their RNA genome into DNA, which then becomes integrated into the host cell's genome. This is a unique characteristic of retroviruses, as most other viruses use DNA as their genetic material.

Retroviruses can cause a variety of diseases in animals and humans, including cancer, neurological disorders, and immunodeficiency syndromes like AIDS. They have a lipid membrane envelope that contains glycoprotein spikes, which allow them to attach to and enter host cells. Once inside the host cell, the viral RNA is reverse transcribed into DNA by the enzyme reverse transcriptase, which is then integrated into the host genome by the enzyme integrase.

Retroviruses can remain dormant in the host genome for extended periods of time, and may be reactivated under certain conditions to produce new viral particles. This ability to integrate into the host genome has also made retroviruses useful tools in molecular biology, where they are used as vectors for gene therapy and other genetic manipulations.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

Accelerated Phase Leukemia, Myeloid is a stage in the progression of certain myeloid malignancies such as Chronic Myelogenous Leukemia (CML) or Myelodysplastic Syndromes (MDS). During this phase, there is an increase in the number of immature blood cells (blasts) in the bone marrow and/or blood compared to the chronic phase. However, it has not yet reached the level of blast proliferation seen in the blast crisis phase.

The accelerated phase is characterized by various laboratory and clinical features, including:
- A significant increase in the percentage of blasts (10-19%) in the peripheral blood or bone marrow
- An increase in the white blood cell count, typically over 50 x 10^9/L
- The presence of new cytogenetic abnormalities or an increasing number of existing chromosomal changes
- A decrease in platelet count and/or hemoglobin levels
- Increasing symptoms related to bone marrow failure, such as fatigue, infection, and bleeding

The accelerated phase often precedes the blast crisis phase, which is associated with a worse prognosis. Early detection and intervention in the accelerated phase may help improve treatment outcomes and delay progression to blast crisis.

3T3 cells are a type of cell line that is commonly used in scientific research. The name "3T3" is derived from the fact that these cells were developed by treating mouse embryo cells with a chemical called trypsin and then culturing them in a flask at a temperature of 37 degrees Celsius.

Specifically, 3T3 cells are a type of fibroblast, which is a type of cell that is responsible for producing connective tissue in the body. They are often used in studies involving cell growth and proliferation, as well as in toxicity tests and drug screening assays.

One particularly well-known use of 3T3 cells is in the 3T3-L1 cell line, which is a subtype of 3T3 cells that can be differentiated into adipocytes (fat cells) under certain conditions. These cells are often used in studies of adipose tissue biology and obesity.

It's important to note that because 3T3 cells are a type of immortalized cell line, they do not always behave exactly the same way as primary cells (cells that are taken directly from a living organism). As such, researchers must be careful when interpreting results obtained using 3T3 cells and consider any potential limitations or artifacts that may arise due to their use.

Myristic acid is not typically considered a medical term, but it is a scientific term related to the field of medicine. It is a type of fatty acid that is found in some foods and in the human body. Medically, it may be relevant in discussions of nutrition, metabolism, or lipid disorders.

Here's a definition of myristic acid from a biological or chemical perspective:

Myristic acid is a saturated fatty acid with the chemical formula CH3(CH2)12CO2H. It is a 14-carbon atom chain with a carboxyl group at one end and a methyl group at the other. Myristic acid occurs naturally in some foods, such as coconut oil, palm kernel oil, and dairy products. It is also found in the structural lipids of living cells, where it plays a role in cell signaling and membrane dynamics.

In the context of medical and biological sciences, a "binding site" refers to a specific location on a protein, molecule, or cell where another molecule can attach or bind. This binding interaction can lead to various functional changes in the original protein or molecule. The other molecule that binds to the binding site is often referred to as a ligand, which can be a small molecule, ion, or even another protein.

The binding between a ligand and its target binding site can be specific and selective, meaning that only certain ligands can bind to particular binding sites with high affinity. This specificity plays a crucial role in various biological processes, such as signal transduction, enzyme catalysis, or drug action.

In the case of drug development, understanding the location and properties of binding sites on target proteins is essential for designing drugs that can selectively bind to these sites and modulate protein function. This knowledge can help create more effective and safer therapeutic options for various diseases.

Karyotyping is a medical laboratory test used to study the chromosomes in a cell. It involves obtaining a sample of cells from a patient, usually from blood or bone marrow, and then staining the chromosomes so they can be easily seen under a microscope. The chromosomes are then arranged in pairs based on their size, shape, and other features to create a karyotype. This visual representation allows for the identification and analysis of any chromosomal abnormalities, such as extra or missing chromosomes, or structural changes like translocations or inversions. These abnormalities can provide important information about genetic disorders, diseases, and developmental problems.

A point mutation is a type of genetic mutation where a single nucleotide base (A, T, C, or G) in DNA is altered, deleted, or substituted with another nucleotide. Point mutations can have various effects on the organism, depending on the location of the mutation and whether it affects the function of any genes. Some point mutations may not have any noticeable effect, while others might lead to changes in the amino acids that make up proteins, potentially causing diseases or altering traits. Point mutations can occur spontaneously due to errors during DNA replication or be inherited from parents.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

A Tumor Stem Cell Assay is not a widely accepted or standardized medical definition. However, in the context of cancer research, a tumor stem cell assay generally refers to an experimental procedure used to identify and isolate cancer stem cells (also known as tumor-initiating cells) from a tumor sample.

Cancer stem cells are a subpopulation of cells within a tumor that are believed to be responsible for driving tumor growth, metastasis, and resistance to therapy. They have the ability to self-renew and differentiate into various cell types within the tumor, making them a promising target for cancer therapies.

A tumor stem cell assay typically involves isolating cells from a tumor sample and subjecting them to various tests to identify those with stem cell-like properties. These tests may include assessing their ability to form tumors in animal models or their expression of specific surface markers associated with cancer stem cells. The goal of the assay is to provide researchers with a better understanding of the biology of cancer stem cells and to develop new therapies that target them specifically.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific regions of DNA. It enables the production of thousands to millions of copies of a particular DNA sequence in a rapid and efficient manner, making it an essential tool in various fields such as molecular biology, medical diagnostics, forensic science, and research.

The PCR process involves repeated cycles of heating and cooling to separate the DNA strands, allow primers (short sequences of single-stranded DNA) to attach to the target regions, and extend these primers using an enzyme called Taq polymerase, resulting in the exponential amplification of the desired DNA segment.

In a medical context, PCR is often used for detecting and quantifying specific pathogens (viruses, bacteria, fungi, or parasites) in clinical samples, identifying genetic mutations or polymorphisms associated with diseases, monitoring disease progression, and evaluating treatment effectiveness.

Pyridones are a class of organic compounds that contain a pyridone ring, which is a heterocyclic ring consisting of a six-membered ring with five carbon atoms and one nitrogen atom, with one oxygen atom attached to the nitrogen atom by a double bond. Pyridones can be found in various natural sources, including plants and microorganisms, and they also have important applications in the pharmaceutical industry as building blocks for drug design and synthesis. Some drugs that contain pyridone rings include antihistamines, anti-inflammatory agents, and antiviral agents.

"Gene rearrangement" is a process that involves the alteration of the order, orientation, or copy number of genes or gene segments within an organism's genome. This natural mechanism plays a crucial role in generating diversity and specificity in the immune system, particularly in vertebrates.

In the context of the immune system, gene rearrangement occurs during the development of B-cells and T-cells, which are responsible for adaptive immunity. The process involves breaking and rejoining DNA segments that encode antigen recognition sites, resulting in a unique combination of gene segments and creating a vast array of possible antigen receptors.

There are two main types of gene rearrangement:

1. V(D)J recombination: This process occurs in both B-cells and T-cells. It involves the recombination of variable (V), diversity (D), and joining (J) gene segments to form a functional antigen receptor gene. In humans, there are multiple copies of V, D, and J segments for each antigen receptor gene, allowing for a vast number of possible combinations.
2. Class switch recombination: This process occurs only in mature B-cells after antigen exposure. It involves the replacement of the constant (C) region of the immunoglobulin heavy chain gene with another C region, resulting in the production of different isotypes of antibodies (IgG, IgA, or IgE) that have distinct effector functions while maintaining the same antigen specificity.

These processes contribute to the generation of a diverse repertoire of antigen receptors, allowing the immune system to recognize and respond effectively to a wide range of pathogens.

Immunoprecipitation (IP) is a research technique used in molecular biology and immunology to isolate specific antigens or antibodies from a mixture. It involves the use of an antibody that recognizes and binds to a specific antigen, which is then precipitated out of solution using various methods, such as centrifugation or chemical cross-linking.

In this technique, an antibody is first incubated with a sample containing the antigen of interest. The antibody specifically binds to the antigen, forming an immune complex. This complex can then be captured by adding protein A or G agarose beads, which bind to the constant region of the antibody. The beads are then washed to remove any unbound proteins, leaving behind the precipitated antigen-antibody complex.

Immunoprecipitation is a powerful tool for studying protein-protein interactions, post-translational modifications, and signal transduction pathways. It can also be used to detect and quantify specific proteins in biological samples, such as cells or tissues, and to identify potential biomarkers of disease.

The GRB2 (Growth Factor Receptor-Bound Protein 2) adaptor protein is a cytoplasmic signaling molecule that plays a crucial role in intracellular signal transduction pathways, particularly those involved in cell growth, differentiation, and survival. It acts as a molecular adapter or scaffold, facilitating the interaction between various proteins to form multi-protein complexes and propagate signals from activated receptor tyrosine kinases (RTKs) to downstream effectors.

GRB2 contains several functional domains, including an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The SH2 domain is responsible for binding to specific phosphotyrosine residues on activated RTKs or other adaptor proteins, while the SH3 domains mediate interactions with proline-rich sequences in partner proteins.

Once GRB2 binds to an activated RTK, it recruits and activates the guanine nucleotide exchange factor SOS (Son of Sevenless), which in turn activates the RAS GTPase. Activated RAS then initiates a signaling cascade involving various kinases such as Raf, MEK, and ERK, ultimately leading to changes in gene expression and cellular responses.

In summary, GRB2 is an essential adaptor protein that facilitates the transmission of signals from activated growth factor receptors to downstream effectors, playing a critical role in regulating various cellular processes.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

CD34 is a type of antigen that is found on the surface of certain cells in the human body. Specifically, CD34 antigens are present on hematopoietic stem cells, which are immature cells that can develop into different types of blood cells. These stem cells are found in the bone marrow and are responsible for producing red blood cells, white blood cells, and platelets.

CD34 antigens are a type of cell surface marker that is used in medical research and clinical settings to identify and isolate hematopoietic stem cells. They are also used in the development of stem cell therapies and transplantation procedures. CD34 antigens can be detected using various laboratory techniques, such as flow cytometry or immunohistochemistry.

It's important to note that while CD34 is a useful marker for identifying hematopoietic stem cells, it is not exclusive to these cells and can also be found on other cell types, such as endothelial cells that line blood vessels. Therefore, additional markers are often used in combination with CD34 to more specifically identify and isolate hematopoietic stem cells.

Neoplastic gene expression regulation refers to the processes that control the production of proteins and other molecules from genes in neoplastic cells, or cells that are part of a tumor or cancer. In a normal cell, gene expression is tightly regulated to ensure that the right genes are turned on or off at the right time. However, in cancer cells, this regulation can be disrupted, leading to the overexpression or underexpression of certain genes.

Neoplastic gene expression regulation can be affected by a variety of factors, including genetic mutations, epigenetic changes, and signals from the tumor microenvironment. These changes can lead to the activation of oncogenes (genes that promote cancer growth and development) or the inactivation of tumor suppressor genes (genes that prevent cancer).

Understanding neoplastic gene expression regulation is important for developing new therapies for cancer, as targeting specific genes or pathways involved in this process can help to inhibit cancer growth and progression.

NIH 3T3 cells are a type of mouse fibroblast cell line that was developed by the National Institutes of Health (NIH). The "3T3" designation refers to the fact that these cells were derived from embryonic Swiss mouse tissue and were able to be passaged (i.e., subcultured) more than three times in tissue culture.

NIH 3T3 cells are widely used in scientific research, particularly in studies involving cell growth and differentiation, signal transduction, and gene expression. They have also been used as a model system for studying the effects of various chemicals and drugs on cell behavior. NIH 3T3 cells are known to be relatively easy to culture and maintain, and they have a stable, flat morphology that makes them well-suited for use in microscopy studies.

It is important to note that, as with any cell line, it is essential to verify the identity and authenticity of NIH 3T3 cells before using them in research, as contamination or misidentification can lead to erroneous results.

Post-translational protein processing refers to the modifications and changes that proteins undergo after their synthesis on ribosomes, which are complex molecular machines responsible for protein synthesis. These modifications occur through various biochemical processes and play a crucial role in determining the final structure, function, and stability of the protein.

The process begins with the translation of messenger RNA (mRNA) into a linear polypeptide chain, which is then subjected to several post-translational modifications. These modifications can include:

1. Proteolytic cleavage: The removal of specific segments or domains from the polypeptide chain by proteases, resulting in the formation of mature, functional protein subunits.
2. Chemical modifications: Addition or modification of chemical groups to the side chains of amino acids, such as phosphorylation (addition of a phosphate group), glycosylation (addition of sugar moieties), methylation (addition of a methyl group), acetylation (addition of an acetyl group), and ubiquitination (addition of a ubiquitin protein).
3. Disulfide bond formation: The oxidation of specific cysteine residues within the polypeptide chain, leading to the formation of disulfide bonds between them. This process helps stabilize the three-dimensional structure of proteins, particularly in extracellular environments.
4. Folding and assembly: The acquisition of a specific three-dimensional conformation by the polypeptide chain, which is essential for its function. Chaperone proteins assist in this process to ensure proper folding and prevent aggregation.
5. Protein targeting: The directed transport of proteins to their appropriate cellular locations, such as the nucleus, mitochondria, endoplasmic reticulum, or plasma membrane. This is often facilitated by specific signal sequences within the protein that are recognized and bound by transport machinery.

Collectively, these post-translational modifications contribute to the functional diversity of proteins in living organisms, allowing them to perform a wide range of cellular processes, including signaling, catalysis, regulation, and structural support.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

A residual neoplasm is a term used in pathology and oncology to describe the remaining abnormal tissue or cancer cells after a surgical procedure or treatment aimed at completely removing a tumor. This means that some cancer cells have been left behind and continue to persist in the body. The presence of residual neoplasm can increase the risk of recurrence or progression of the disease, as these remaining cells may continue to grow and divide.

Residual neoplasm is often assessed during follow-up appointments and monitoring, using imaging techniques like CT scans, MRIs, or PET scans, and sometimes through biopsies. The extent of residual neoplasm can influence the choice of further treatment options, such as additional surgery, radiation therapy, chemotherapy, or targeted therapies, to eliminate the remaining cancer cells and reduce the risk of recurrence.

Bone marrow is the spongy tissue found inside certain bones in the body, such as the hips, thighs, and vertebrae. It is responsible for producing blood-forming cells, including red blood cells, white blood cells, and platelets. There are two types of bone marrow: red marrow, which is involved in blood cell production, and yellow marrow, which contains fatty tissue.

Red bone marrow contains hematopoietic stem cells, which can differentiate into various types of blood cells. These stem cells continuously divide and mature to produce new blood cells that are released into the circulation. Red blood cells carry oxygen throughout the body, white blood cells help fight infections, and platelets play a crucial role in blood clotting.

Bone marrow also serves as a site for immune cell development and maturation. It contains various types of immune cells, such as lymphocytes, macrophages, and dendritic cells, which help protect the body against infections and diseases.

Abnormalities in bone marrow function can lead to several medical conditions, including anemia, leukopenia, thrombocytopenia, and various types of cancer, such as leukemia and multiple myeloma. Bone marrow aspiration and biopsy are common diagnostic procedures used to evaluate bone marrow health and function.

The cytoskeleton is a complex network of various protein filaments that provides structural support, shape, and stability to the cell. It plays a crucial role in maintaining cellular integrity, intracellular organization, and enabling cell movement. The cytoskeleton is composed of three major types of protein fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. These filaments work together to provide mechanical support, participate in cell division, intracellular transport, and help maintain the cell's architecture. The dynamic nature of the cytoskeleton allows cells to adapt to changing environmental conditions and respond to various stimuli.

HL-60 cells are a type of human promyelocytic leukemia cell line that is commonly used in scientific research. They are named after the hospital where they were first isolated, the Hospital of the University of Pennsylvania (HUP) and the 60th culture attempt to grow these cells.

HL-60 cells have the ability to differentiate into various types of blood cells, such as granulocytes, monocytes, and macrophages, when exposed to certain chemical compounds or under specific culturing conditions. This makes them a valuable tool for studying the mechanisms of cell differentiation, proliferation, and apoptosis (programmed cell death).

HL-60 cells are also often used in toxicity studies, drug discovery and development, and research on cancer, inflammation, and infectious diseases. They can be easily grown in the lab and have a stable genotype, making them ideal for use in standardized experiments and comparisons between different studies.

'Drosophila proteins' refer to the proteins that are expressed in the fruit fly, Drosophila melanogaster. This organism is a widely used model system in genetics, developmental biology, and molecular biology research. The study of Drosophila proteins has contributed significantly to our understanding of various biological processes, including gene regulation, cell signaling, development, and aging.

Some examples of well-studied Drosophila proteins include:

1. HSP70 (Heat Shock Protein 70): A chaperone protein involved in protein folding and protection from stress conditions.
2. TUBULIN: A structural protein that forms microtubules, important for cell division and intracellular transport.
3. ACTIN: A cytoskeletal protein involved in muscle contraction, cell motility, and maintenance of cell shape.
4. BETA-GALACTOSIDASE (LACZ): A reporter protein often used to monitor gene expression patterns in transgenic flies.
5. ENDOGLIN: A protein involved in the development of blood vessels during embryogenesis.
6. P53: A tumor suppressor protein that plays a crucial role in preventing cancer by regulating cell growth and division.
7. JUN-KINASE (JNK): A signaling protein involved in stress response, apoptosis, and developmental processes.
8. DECAPENTAPLEGIC (DPP): A member of the TGF-β (Transforming Growth Factor Beta) superfamily, playing essential roles in embryonic development and tissue homeostasis.

These proteins are often studied using various techniques such as biochemistry, genetics, molecular biology, and structural biology to understand their functions, interactions, and regulation within the cell.

Aniline compounds, also known as aromatic amines, are organic compounds that contain a benzene ring substituted with an amino group (-NH2). Aniline itself is the simplest and most common aniline compound, with the formula C6H5NH2.

Aniline compounds are important in the chemical industry and are used in the synthesis of a wide range of products, including dyes, pharmaceuticals, and rubber chemicals. They can be produced by reducing nitrobenzene or by directly substituting ammonia onto benzene in a process called amination.

It is important to note that aniline compounds are toxic and can cause serious health effects, including damage to the liver, kidneys, and central nervous system. They can also be absorbed through the skin and are known to have carcinogenic properties. Therefore, appropriate safety measures must be taken when handling aniline compounds.

Phosphoproteins are proteins that have been post-translationally modified by the addition of a phosphate group (-PO3H2) onto specific amino acid residues, most commonly serine, threonine, or tyrosine. This process is known as phosphorylation and is mediated by enzymes called kinases. Phosphoproteins play crucial roles in various cellular processes such as signal transduction, cell cycle regulation, metabolism, and gene expression. The addition or removal of a phosphate group can activate or inhibit the function of a protein, thereby serving as a switch to control its activity. Phosphoproteins can be detected and quantified using techniques such as Western blotting, mass spectrometry, and immunofluorescence.

Human chromosome pair 12 consists of two rod-shaped structures present in the nucleus of each cell in the human body. Each chromosome is made up of DNA tightly coiled around histone proteins, forming a complex structure called a chromatin.

Chromosomes come in pairs, with one chromosome inherited from each parent. In humans, there are 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. Chromosome pair 12 is the 12th pair of autosomal chromosomes, meaning they are not sex chromosomes (X or Y).

Chromosome 12 is a medium-sized chromosome and contains an estimated 130 million base pairs of DNA. It contains around 1,200 genes that provide instructions for making proteins and regulating various cellular processes. Some of the genes located on chromosome 12 include those involved in metabolism, development, and response to environmental stimuli.

Abnormalities in chromosome 12 can lead to genetic disorders, such as partial trisomy 12q, which is characterized by an extra copy of the long arm of chromosome 12, and Jacobsen syndrome, which is caused by a deletion of the distal end of the long arm of chromosome 12.

Proto-oncogenes are normal genes that are present in all cells and play crucial roles in regulating cell growth, division, and death. They code for proteins that are involved in signal transduction pathways that control various cellular processes such as proliferation, differentiation, and survival. When these genes undergo mutations or are activated abnormally, they can become oncogenes, which have the potential to cause uncontrolled cell growth and lead to cancer. Oncogenes can contribute to tumor formation through various mechanisms, including promoting cell division, inhibiting programmed cell death (apoptosis), and stimulating blood vessel growth (angiogenesis).

Southern blotting is a type of membrane-based blotting technique that is used in molecular biology to detect and locate specific DNA sequences within a DNA sample. This technique is named after its inventor, Edward M. Southern.

In Southern blotting, the DNA sample is first digested with one or more restriction enzymes, which cut the DNA at specific recognition sites. The resulting DNA fragments are then separated based on their size by gel electrophoresis. After separation, the DNA fragments are denatured to convert them into single-stranded DNA and transferred onto a nitrocellulose or nylon membrane.

Once the DNA has been transferred to the membrane, it is hybridized with a labeled probe that is complementary to the sequence of interest. The probe can be labeled with radioactive isotopes, fluorescent dyes, or chemiluminescent compounds. After hybridization, the membrane is washed to remove any unbound probe and then exposed to X-ray film (in the case of radioactive probes) or scanned (in the case of non-radioactive probes) to detect the location of the labeled probe on the membrane.

The position of the labeled probe on the membrane corresponds to the location of the specific DNA sequence within the original DNA sample. Southern blotting is a powerful tool for identifying and characterizing specific DNA sequences, such as those associated with genetic diseases or gene regulation.

Nitriles, in a medical context, refer to a class of organic compounds that contain a cyano group (-CN) bonded to a carbon atom. They are widely used in the chemical industry and can be found in various materials, including certain plastics and rubber products.

In some cases, nitriles can pose health risks if ingested, inhaled, or come into contact with the skin. Short-term exposure to high levels of nitriles can cause irritation to the eyes, nose, throat, and respiratory tract. Prolonged or repeated exposure may lead to more severe health effects, such as damage to the nervous system, liver, and kidneys.

However, it's worth noting that the medical use of nitriles is not very common. Some nitrile gloves are used in healthcare settings due to their resistance to many chemicals and because they can provide a better barrier against infectious materials compared to latex or vinyl gloves. But beyond this application, nitriles themselves are not typically used as medications or therapeutic agents.

Adamantane is a chemical compound with the formula C10H16. It is a hydrocarbon that consists of a cage-like structure of carbon atoms, making it one of the simplest diamondoid compounds. The term "adamantane" is also used more broadly to refer to any compound that contains this characteristic carbon cage structure.

In the context of medicine, adamantane derivatives are a class of antiviral drugs that have been used to treat and prevent influenza A infections. These drugs work by binding to the M2 protein of the influenza virus, which is essential for viral replication. By blocking the function of this protein, adamantane derivatives can prevent the virus from multiplying within host cells.

Examples of adamantane derivatives used in medicine include amantadine and rimantadine. These drugs are typically administered orally and have been shown to be effective at reducing the severity and duration of influenza A symptoms, particularly when used early in the course of infection. However, resistance to these drugs has become increasingly common among circulating strains of influenza A virus, which has limited their usefulness in recent years.

Leukemia, lymphoid is a type of cancer that affects the lymphoid cells, which are a vital part of the body's immune system. It is characterized by the uncontrolled production of abnormal white blood cells (leukocytes or WBCs) in the bone marrow, specifically the lymphocytes. These abnormal lymphocytes accumulate and interfere with the production of normal blood cells, leading to a decrease in red blood cells (anemia), platelets (thrombocytopenia), and healthy white blood cells (leukopenia).

There are two main types of lymphoid leukemia: acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Acute lymphoblastic leukemia progresses rapidly, while chronic lymphocytic leukemia has a slower onset and progression.

Symptoms of lymphoid leukemia may include fatigue, frequent infections, easy bruising or bleeding, weight loss, swollen lymph nodes, and bone pain. Treatment options depend on the type, stage, and individual patient factors but often involve chemotherapy, radiation therapy, targeted therapy, immunotherapy, or stem cell transplantation.

Neoplastic stem cells, also known as cancer stem cells (CSCs), are a subpopulation of cells within a tumor that are capable of self-renewal and generating the heterogeneous lineages of cells that comprise the tumor. These cells are believed to be responsible for the initiation, maintenance, and progression of cancer, as well as its recurrence and resistance to therapy.

CSCs share some similarities with normal stem cells, such as their ability to divide asymmetrically and give rise to differentiated progeny. However, they also have distinct characteristics that distinguish them from their normal counterparts, including aberrant gene expression, altered signaling pathways, and increased resistance to apoptosis (programmed cell death).

The existence of CSCs has important implications for cancer diagnosis, treatment, and prevention. Targeting these cells specifically may be necessary to achieve durable remissions and prevent relapse, as they are thought to survive conventional therapies that target the bulk of the tumor. Further research is needed to better understand the biology of CSCs and develop effective strategies for their elimination.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

The platelet-derived growth factor beta (PDGF-β) receptor is a type of cell surface receptor that binds to specific proteins called platelet-derived growth factors (PDGFs). PDGFs are important signaling molecules involved in various biological processes, including cell growth, division, and survival.

The PDGF-β receptor is a transmembrane protein with an extracellular domain that binds to PDGFs and an intracellular domain that activates downstream signaling pathways when activated by PDGF binding. The PDGF-BB isoform specifically binds to the PDGF-β receptor, leading to its activation and initiation of signaling cascades that promote cell proliferation, migration, and survival.

Mutations in the PDGF-β receptor gene have been associated with certain types of cancer and vascular diseases, highlighting its importance in regulating cell growth and division. Inhibitors of the PDGF-β receptor have been developed as potential therapeutic agents for the treatment of various cancers and other diseases.

Precursor B-cell Acute Lymphoblastic Leukemia/Lymphoma (also known as Precursor B-cell ALL or Precursor B-cell Non-Hodgkin Lymphoma) is a type of cancer that affects the early stages of B-cell development. It is characterized by the uncontrolled proliferation of immature B-cells, also known as lymphoblasts, in the bone marrow, blood, and sometimes in other organs such as the lymph nodes. These malignant cells accumulate and interfere with the normal production of blood cells, leading to symptoms such as anemia, infection, and bleeding.

The distinction between Precursor B-cell ALL and Precursor B-cell Lymphoma is based on the site of involvement. If the majority of the cancerous cells are found in the bone marrow and/or blood, it is classified as a leukemia (ALL). However, if the malignant cells primarily involve the lymph nodes or other extramedullary sites, it is considered a lymphoma. Despite this distinction, both entities share similar biological features, treatment approaches, and prognoses.

It's important to note that medical definitions can vary slightly based on the source and context. For the most accurate information, consult authoritative resources such as medical textbooks or peer-reviewed articles.

Drug synergism is a pharmacological concept that refers to the interaction between two or more drugs, where the combined effect of the drugs is greater than the sum of their individual effects. This means that when these drugs are administered together, they produce an enhanced therapeutic response compared to when they are given separately.

Drug synergism can occur through various mechanisms, such as:

1. Pharmacodynamic synergism - When two or more drugs interact with the same target site in the body and enhance each other's effects.
2. Pharmacokinetic synergism - When one drug affects the metabolism, absorption, distribution, or excretion of another drug, leading to an increased concentration of the second drug in the body and enhanced therapeutic effect.
3. Physiochemical synergism - When two drugs interact physically, such as when one drug enhances the solubility or permeability of another drug, leading to improved absorption and bioavailability.

It is important to note that while drug synergism can result in enhanced therapeutic effects, it can also increase the risk of adverse reactions and toxicity. Therefore, healthcare providers must carefully consider the potential benefits and risks when prescribing combinations of drugs with known or potential synergistic effects.

A precipitin test is a type of immunodiagnostic test used to detect and measure the presence of specific antibodies or antigens in a patient's serum. The test is based on the principle of antigen-antibody interaction, where the addition of an antigen to a solution containing its corresponding antibody results in the formation of an insoluble immune complex known as a precipitin.

In this test, a small amount of the patient's serum is added to a solution containing a known antigen or antibody. If the patient has antibodies or antigens that correspond to the added reagent, they will bind and form a visible precipitate. The size and density of the precipitate can be used to quantify the amount of antibody or antigen present in the sample.

Precipitin tests are commonly used in the diagnosis of various infectious diseases, autoimmune disorders, and allergies. They can also be used in forensic science to identify biological samples. However, they have largely been replaced by more modern immunological techniques such as enzyme-linked immunosorbent assays (ELISAs) and radioimmunoassays (RIAs).

Acute Megakaryoblastic Leukemia (AMKL) is a type of cancer that affects the blood and bone marrow. Specifically, it is a subtype of acute myeloid leukemia (AML), which is characterized by the rapid growth of abnormal cells in the bone marrow that interfere with the production of normal blood cells.

In AMKL, the abnormal cells are megakaryoblasts, which are immature cells that should develop into platelet-producing cells called megakaryocytes. However, in AMKL, these cells do not mature properly and instead accumulate in the bone marrow and bloodstream, leading to a shortage of healthy blood cells.

Symptoms of AMKL may include fatigue, weakness, frequent infections, easy bruising or bleeding, and the appearance of small red spots on the skin (petechiae). Diagnosis typically involves a combination of physical exam, medical history, blood tests, bone marrow aspiration and biopsy, and sometimes imaging studies.

Treatment for AMKL usually involves a combination of chemotherapy, radiation therapy, and/or stem cell transplantation. The specific treatment plan will depend on several factors, including the patient's age, overall health, and the extent of the disease.

This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in ... c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral ... is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity". Genes Dev. 11 (19): 2456-67. ... gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows ...
"Entrez Gene: Cdk5 and Abl enzyme substrate 2". Retrieved 2017-03-20. Matsuoka M, Sudo H, Tsuji K, Sato H, Kurita M, Suzuki H, ... Cdk5 and Abl enzyme substrate 2 is a protein that in humans is encoded by the CABLES2 gene. GRCh38: Ensembl release 89: ... v t e (Articles with short description, Short description matches Wikidata, Genes on human chromosome 20, All stub articles, ...
Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene. Abl ... "Entrez Gene: ABI1 abl-interactor 1". Tani K, Sato S, Sukezane T, Kojima H, Hirose H, Hanafusa H, Shishido T (June 2003). "Abl ... 1998). "ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23 ... ABI1 human gene location in the UCSC Genome Browser. ABI1 human gene details in the UCSC Genome Browser. v t e (Articles with ...
"Entrez Gene: ABI2 abl interactor 2". Cao C, Leng Y, Li C, Kufe D (April 2003). "Functional interaction between the c-Abl and ... a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity". Genes Dev. ... Abl interactor 2 also known as Abelson interactor 2 (Abi-2) is a protein that in humans is encoded by the ABI2 gene. ABI2 has ... ABI2 human gene location in the UCSC Genome Browser. ABI2 human gene details in the UCSC Genome Browser. v t e (Articles with ...
Stephan, Gene (19 May 2011). "Heat to take on Asia's best teams". The West Australian. Seven West Media Limited. Archived from ... "2011 ABL All-Star Game Boxscore". Australian Baseball League. 21 December 2011. Archived from the original on 16 April 2014. ... The Perth Heat defeated the Aces two games to one in the championship series, to win back-to-back ABL championships. Announced ... The Asia Series is held in November, which would otherwise create a conflict for the ABL champion team as the following season ...
"Entrez Gene: CABLES1 Cdk5 and Abl enzyme substrate 1". Human CABLES1 genome location and CABLES1 gene details page in the UCSC ... CDK5 and ABL1 enzyme substrate 1 is a protein that in humans is encoded by the CABLES1 gene. CABLES1 is a cyclin-dependent ... Sato H, Nishimoto I, Matsuoka M (2002). "ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl". Biochim ... 2007). "NESH (Abi-3) is present in the Abi/WAVE complex but does not promote c-Abl-mediated phosphorylation". FEBS Lett. 580 ( ...
... has been shown to interact with Abl gene. ENSG00000288283 GRCh38: Ensembl release 89: ENSG00000132005, ENSG00000288283 - ... The RFX1 gene is a member of the regulatory factor X (RFX) gene family, which encodes transcription factors that contain five ... Agami R, Shaul Y (April 1998). "The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a ... "Entrez Gene: RFX1 regulatory factor X, 1 (influences HLA class II expression)". Emery P, Durand B, Mach B, Reith W (March 1996 ...
... has been shown to interact with Abl gene, BCR gene, C-Raf, c-Kit, Insulin receptor,> Insulin-like growth factor 1 ... 1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201- ... "Entrez Gene: GRB10 growth factor receptor-bound protein 10". Jerome CA, Scherer SW, Tsui LC, Gietz RD, Triggs-Raine B (February ... This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor ...
Often, fusion genes are oncogenes that cause cancer; these include BCR-ABL, TEL-AML1 (ALL with t(12 ; 21)), AML1-ETO (M2 AML ... Chimeric gene De novo gene birth ETV6-NTRK3 gene fusion Exon shuffling Gene duplication Horizontal gene transfer List of RNA- ... Gene fusion plays a key role in the evolution of gene architecture. We can observe its effect if gene fusion occurs in coding ... A fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, ...
This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that ... Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (February 1996). "p210BCR/ABL induces formation of complexes containing focal ... The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. PIK3CG has been ... "Entrez Gene: PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide". Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, ...
... has been shown to interact with three proteins: Abl gene, catalase, and SORBS2. The protein Abl gene is also known as ... "Entrez Gene: ABL2 v-abl Abelson murine leukemia viral oncogene homolog 2 (arg, Abelson-related gene)". Nagy, Ádám; Pongor, ... Genes,+abl at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Abelson+Leukemia+Virus at the U.S. National ... 1987). "A novel human gene closely related to the abl proto-oncogene". Science. 234 (4783): 1545-8. doi:10.1126/science.3787260 ...
... has been shown to interact with Abl gene. GRCh38: Ensembl release 89: ENSG00000163554 - Ensembl, May 2017 ... This gene is one member of a family of alpha-spectrin genes. The encoded protein is primarily composed of 22 spectrin repeats ... "Entrez Gene: SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2)". Ziemnicka-Kotula, D; Xu J; Gu H; Potempska A; Kim K S; ... Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis type 2, ...
"Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells". Genes, Chromosomes & Cancer. 46 (1): 67-74. doi: ... "Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL oncogene". Genes, Chromosomes & Cancer. 32 (4): 353-63 ... "Entrez Gene: BACH2 BTB and CNC homology 1, basic leucine zipper transcription factor 2". Rosbrook GO, Stead MA, Carr SB, Wright ... Yoshida C, Yoshida F, Sears DE, Hart SM, Ikebe D, Muto A, Basu S, Igarashi K, Melo JV (February 2007). "Bcr-Abl signaling ...
This results in the fusion of the genes BCR and ABL. This atypical gene fusion encodes for unregulated tyrosine kinase activity ... rather than solely focusing on one gene. It can provide insight into additional information such as gene-gene interactions, ... However, after imatinib was used as the first-line therapy, several BCR-ABL-dependent and BCR-ABL-independent mechanisms of ... Cancer is a genetic disease where changes to genes can cause cells to grow and divide out of control. Each cancer can have a ...
... has been shown to interact with the ABL2 and Abl genes. Infection with the murine leukemia virus causes catalase ... Cao C, Leng Y, Kufe D (August 2003). "Catalase activity is regulated by c-Abl and Arg in the oxidative stress response". The ... Brioukhanov AL, Netrusov AI, Eggen RI (June 2006). "The catalase and superoxide dismutase genes are transcriptionally up- ... Queens have more than two times higher catalase activity and seven times higher expression levels of the catalase gene RsCAT1 ...
TPP36 isoforms have been found to be substrates of Abl tyrosine kinase. The CDV3 gene is on chromosome 3 (3q22.1). There were ... CDV3 has been considered as a potential target for gene therapy. Related gene families include plasma proteins and predicted ... "CDV3 CDV3 homolog [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-17. "Nucleotide Links for Gene ... Protein CDV3 homolog also known as carnitine deficiency-associated gene expressed in ventricle 3 is a protein that in humans is ...
... as a BCR/ABL-inducible gene". FEBS Letters. 466 (2-3): 367-71. doi:10.1016/S0014-5793(00)01112-1. PMID 10682862. S2CID 26778464 ... Five alternatively spliced transcript variants encoding the same protein have been observed for this gene. This gene encodes an ... van Baren N, Chambost H, Ferrant A, Michaux L, Ikeda H, Millard I, Olive D, Boon T, Coulie PG (Sep 1998). "PRAME, a gene ... "Entrez Gene: PRAME preferentially expressed antigen in melanoma". Al-Khadairi G, Decock J (July 2019). "Cancer Testis Antigens ...
Gene Cards. Retrieved 1 May 2018. "PPP2R5C". Gene Cards. Retrieved 1 May 2018. Grueber, Emileigh K. (2013). "Role of ABL Family ... The FAM43A gene has been identified in cDNA screening as a possible cancer development and progression candidate gene. ... involved the screening of 906 K SNPs within the genome to identify possible candidate genes, with FAM43A being the closest gene ... FAM43A shows predicted interaction with the Abelson (ABL) kinase, and ABL members link diverse extracellular stimuli to ...
Bcr-Abl was regarded as highly attractive target for drug intervention since the Bcr-Abl fusion gene encodes a constitutively ... Bcr-Abl dependent mechanisms include over expression or amplification of the Bcr-Abl gene and point mutations within the Bcr- ... gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has ... base pair substitution at position 944 of the Abl gene (codon '315' of the Abl protein) sequence resulting in amino acid ...
T(9;22) affect the ABL gene at 9q34 and BCR at 22q11. The hybrid gene product ABL/BCR is an oncogene which could lead several ... BCR/ABL pathway could also active PI64K/Akt/STAT5 pathway which has anti-apoptotic activity. BCR/ABL induce cell adhesive and ... ABL/BCR could active several molecular pathways: RAS signaling could be activated by BCR/ABL by GRB2 adaptor which interact ... Some focal adhesion complex (PAXILLIN, FAK0 could be activated by BCR/ABL with adaptor molecule CRK-L. BCR/ABL could inactivate ...
Staverman played in the ABL in between. The New York Knicks traded Darrall Imhoff and cash to the Detroit Pistons for Gene Shue ... The Chicago Zephyrs traded Gene Conley to the New York Knicks for Phil Jordon and Cliff Luyk. The Chicago Zephyrs signed Johnny ...
Most importantly, the Philadelphia chromosome and other BCR/ABL fusion genes are not detected. Peripheral blood neutrophilia ... and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene. The most common clinical finding is hepatosplenomegaly ... See OHSU 2013 findings of gene CSF3R, mutation p. T6181 This is a rare disease, with less than 100 cases reported. Of these ...
This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may ... This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this ... Suppression of tumorigenicity 5 is a protein that in humans is encoded by the ST5 gene. ST5 orthologs have been identified in ... "Entrez Gene: ST5 suppression of tumorigenicity 5". "OrthoMaM phylogenetic marker: ST5 coding sequence". Lichy JH, Majidi M, ...
Wilda M, Fuchs U, Wössmann W, Borkhardt A (August 2002). "Killing of leukemic cells with a BCR/ABL fusion gene by RNA ... Recently, it has been discovered that small RNA can trigger specific gene silencing in human cells. The RNAi reaction enables a ... and the resulting RNAi has been extremely successful in focusing on target genes. When delivering siRNA to deep tissue layers ... and abnormalities in processing target genes and proteins. Recent evidence shows that miRNAs play an important role in human ...
"Entrez Gene: RIN1 Ras and Rab interactor 1". Mitin, Natalia Y; Ramocki Melissa B; Zullo Alfred J; Der Channing J; Konieczny ... Hu H, Bliss JM, Wang Y, Colicelli J (2005). "RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell ... Ras and Rab interactor 1 is a protein that in humans is encoded by the RIN1 gene. RIN1 has been shown to interact with HRAS. ... 1997). "Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1". Immunity. 6 (6): 773-82. ...
"Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase". The Journal of Biological ... "Entrez Gene: ENAH enabled homolog (Drosophila)". Tani K, Sato S, Sukezane T, Kojima H, Hirose H, Hanafusa H, Shishido T (June ... Protein enabled homolog is a protein that in humans is encoded by the ENAH gene. ENAH has been shown to interact with ABI1, ZYX ... Sazuka T, Tomooka Y, Kathju S, Ikawa Y, Noda M, Kumar S (October 1992). "Identification of a developmentally regulated gene in ...
Genes Immun. 4 (1): 40-5. doi:10.1038/sj.gene.6363891. PMID 12595900. "Entrez Gene: DOK3 docking protein 3". Cong F, Yuan B, ... Goff SP (2000). "Characterization of a Novel Member of the DOK Family That Binds and Modulates Abl Signaling". Mol. Cell. Biol ... Favre C, Gerard A, Clauzier E, Pontarotti P, Olive D, Nunes JA (Feb 2003). "DOK4 and DOK5: new Dok-related genes expressed in ... Docking protein 3 is a protein that in humans is encoded by the DOK3 gene. GRCh38: Ensembl release 89: ENSG00000146094 - ...
... has been shown to interact with: Abl gene, BCAR1, BCR gene, CBLB, CD117, CD34, Cbl gene, Dock2, EPOR, GAB1, GAB2, INPP5D, ... It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL. In addition, CRKL ... Kolibaba KS, Bhat A, Heaney C, Oda T, Druker BJ (March 1999). "CRKL binding to BCR-ABL and BCR-ABL transformation". Leukemia & ... "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation". Blood. 89 (1): 297-306. doi:10.1182/blood.V89.1. ...
November 2003). "T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expression". PLOS Biol ... Mutations in this gene have been associated to cases of focal epilepsy (doi:10.1038/ng.2601). In Homo sapiens, the DEPDC5 gene ... It is encoded by a gene of the same name, located on chromosome 22. The function of DEPDC5 is not yet known, but it has been ... November 2006). "Global mapping of c-Myc binding sites and target gene networks in human B cells". Proc. Natl. Acad. Sci. U.S.A ...
The results of the study support the role of c-Abl and HDAC2 in the signaling pathway of gene expression in patients with ... October 2014). "c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's ... "Entrez Gene: HDAC2 histone deacetylase 2". Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, et al. (March 2007). "Hdac2 ... This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein ...
While human nck-1 gene has been localised to the 3q21 locus of chromosome 3, the nck-2 gene can be found on chromosome 2 at the ... Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding ... The nck gene was initially isolated from a human melanoma cDNA library using a monoclonal antibody produced against the human ... Chen M, She H, Davis EM, Spicer CM, Kim L, Ren R, Le Beau MM, Li W (October 1998). "Identification of Nck family genes, ...
This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in ... c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral ... is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity". Genes Dev. 11 (19): 2456-67. ... gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows ...
CABLES1 Cdk5 and Abl enzyme substrate 1 [Homo sapiens] CABLES1 Cdk5 and Abl enzyme substrate 1 [Homo sapiens]. Gene ID:91768 ... Gene neighbors Overlapping genes and two nearest non-overlapping genes on either side ... Gene. Interaction. Pubs. Vif vif HIV-1 Vif upregulates the expression of Cdk5 and Abl enzyme substrate 1 (CABLES1) in Vif- ... CABLES1 Cdk5 and Abl enzyme substrate 1 [ Homo sapiens (human) ] Gene ID: 91768, updated on 7-Sep-2023 ...
v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene). v-abl Abelson murine leukemia viral oncogene ... Gene neighbors Overlapping genes and two nearest non-overlapping genes on either side ... Abl2 ABL proto-oncogene 2, non-receptor tyrosine kinase [ Mus musculus (house mouse) ] Gene ID: 11352, updated on 23-Nov-2023 ... Overexpression of Abl-related gene tyrosine kinase ABL2 in pro-B cell line Ba/F3 cells expressing an oncogenic mutant of FLT3 ( ...
Catalog of Genes and Diseases from OMIM. *ABETALIPOPROTEINEMIA; ABL. Scientific Articles on PubMed. *PubMed ... Gene. 2013 Jan 1;512(1):28-34. doi: 10.1016/j.gene.2012.09.117. Epub 2012 Oct 6. Citation on PubMed ... Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function and ... Abetalipoproteinemia is caused by mutations in the MTTP gene, which provides instructions for making a protein called ...
BCR gene fused ABL kinase may be the critical traveling pressure. * Post author By molecularcircuit ... BCR gene fused ABL kinase may be the critical traveling pressure for the Philadelphia Chromosome positive (Ph+) Chronic Myeloid ... The various other important level of resistance mechanism is because of the amplification from the BCR-ABL gene [10]. Several ... First magnification 200). Dialogue Imatinib, the initial launched focus on therapy, which potently inhibits BCR-ABL, c-KIT and ...
Jardan C, Jardan D, Coriu D, Severin E. Atypical patterns of BCR/ABL gene rearrangements by interphase fluorescence in situ ... In 71 out of 83 cases the typical interphase FISH signal patterns of BCR/ABL gene rearrangements was identified - one red ... Atypical patterns of BCR/ABL gene rearrangements by interphase fluorescence in situ hybridization (FISH) in patients with ... Fluorescent in situ hybridization (FISH) technique is increasingly used for the identification of BCR/ABL gene rearrangements in ...
The fusion BCR/ABL gene is usually observed at the der(22) chromosome while atypical rearrangements in CML patients are rare. ... The fusion BCR/ABL gene is usually observed at the der(22) chromosome while atypical rearrangements in CML patients are rare. ... Key words: Variant pH translocations, pH chromosome, BCR/ABL, FISH, chronic myeloid leukemia. ... Key words: Variant pH translocations, pH chromosome, BCR/ABL, FISH, chronic myeloid leukemia. ...
The Abelson murine leukaemia (ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. This ... In the present study, in silico prediction of MAR/SAR was performed in the ABL gene. More than 80% of the predicted MAR/SAR ... study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress- ... induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that ...
Inhibition of bcr-abl oncogene expression by novel deoxyribozymes (DNAzymes). Hum Gene Ther 10, 2847-2857 (1999). ... The output of the system (the target gene) is programmable and is selected by the RNA-binding arms sequence. Since both output ... Benenson, Y., Gil, B., Ben-Dor, U., Adar, R. & Shapiro, E. An autonomous molecular computer for logical control of gene ... Unlike previous systems13 which rely on gene transcription to perform computation, our computing element directly binds to both ...
It carries a new gene called bcr-abl, which sets off a process that creates abnormal white blood cells. ... Polymerase chain reaction (PCR) test to look for the bcr-abl gene ... They carry genes, which tell your cells what to do. When you ... They kill off CML blood cells by blocking the protein made by the abnormal gene bcr-abl. You may have side effects like rashes ... None of the abnormal gene can be found in your blood. Being in remission isnt the same as being cured. The cancer can return. ...
The ABL oncogene encodes a tyrosine protein kinase. The resulting BCR-ABL fusion gene encodes a chimeric protein with strong ... gene regions in green. The abnormal bcr/abl fusion present in Philadelphia chromosome-positive cells is in yellow (right panel ... Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q (c-abl to a specific breakpoint cluster ... Shown is the result of the reciprocal translocation of 22q to the lower arm of 9 and 9q (c-abl to a specific breakpoint cluster ...
A diagram showing the major cancer genes for some cancers. The larger the ... BCR/ABL. New protein created by fusion of bcr and abl triggers unregulated cell growth. Chronic myelogenous and acute lymphotic ... Cancer Genes A diagram showing the major cancer genes for some cancers. The larger the gene name, the more frequently that gene ... This process can involve large amounts of DNA and can affect many genes. The movement of a gene or group of genes to a ...
Gene ratio test for four genes. 1) persons suspected of having mesothelioma 2) Mesothelioma patients. 1) Diagnosis and 2) ... BCR/ABL. Individuals with a diagnosis, clinical suspicion or family history of CML. Diagnosis and treatment monitoring. ... gene expression. Persons with suspected lung cancer. Diagnosis of lung cancer. Lung Cancer. PI3K. Patients suffering from lung ... Gene Expression. Heart Transplant Patients. Risk Assessment for low/moderate ACR. Acute Lymphoblastic Leukemia (ALL). TPMT. ...
BCR-ABL micro-breakpoint cluster region. Gene Type: biological-region Organism: Homo sapiens Chromosome: 22 NCBI GeneID: ...
Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration. ... Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative ... Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin ...
The non-fusion isoforms of the ABL gene (ABLa and ABLb) were scarcely detected compared with the mutant BCR-ABL fusion ... Hand gating shows that single-cell RNA expression from the BCR-ABL fusion gene transcript is correlated to the proportion of ... We also demonstrated the ability to detect a BCL-ABL fusion gene transcript associated with CML and reliably detected ... BCR-ABL primers flank the fusion junction while ABLa and ABLb primers flank the non-fusion ABL isoforms at the fusion junction ...
The translocation creates a new, fused gene (called BCR-ABL), that produces a cancer-causing enzyme called Bcr-Abl. Bcr-Abl ... If the disease is discovered early, it almost always responds to the drug Gleevec, which puts the brakes on Bcr-Abl activity. ... Perrotti said his studies show that it may be due to the increased activity of Bcr-Abl itself. ... But starting treatment again with forskolin - even weeks after initial treatment had stopped - blocked Bcr-Abl activity and ...
... in which the ABL gene is mistakenly joined to the BCR gene, forming a mutated BCR-ABL "fusion gene." The BCR-ABL gene leads to ... Ponatinib is often used to treat CML that has a specific additional alteration in the BCR-ABL gene known as T315I, which makes ... PF-114 is an inhibitor of the mutated BCR-ABL gene and is active against Philadelphia chromosome-positive leukemias, and may be ... Taken as a pill once or twice daily, TKIs target the protein made by the mutated BCR-ABL fusion gene. ...
Low PU.1 expression in AML may account for low ATG gene expression in this disease. Low expression of the autophagy initiator ... We found a significantly lower expression of key autophagy- (ATG-) related genes in primary AML as compared to healthy ... data represent log2 expression levels and were normalized to the expression levels of the 2 housekeeping genes HMBS and ABL. ... Values were normalized to the expression levels of the housekeeping genes HMBS and ABL1. Mann-Whitney U test, , , , . ...
6. Targeted gene disruption of the endogenous c-abl locus by homologous recombination with DNA encoding a selectable fusion ... Abl-interactor-1, A Novel SH3 Protein Binding to the Carboxy-terminal Portion of the Abl Protein, Suppresses v-abl Transforming ... C-Abl Is Required for the Development of Hyperoxia-Induced Retinopathy Nunes, Irene; Zanetta, Lucia; Higgins, Rosemary D.; ... Distinct Roles of c-Abl and Atm in Oxidative Stress Response Are Mediated by Protein Kinase C δ Goff, Stephen P.; Nakayama, ...
They identified six novel genes: PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2. Of these genes, PPP6C, RAC1, and STK19 are ... Notable examples include imatinib (BCR-ABL) and trastuzumab (HER2). Targeted therapies have the potential to be more effective ... The investigation searched for mutations capable of altering gene function and identified the FLT3 gene as a distinguishing ... BRCA genes (Kurian et al., 2014). The use of NGS in clinical diagnostics may be separated into three approaches: gene panels, ...
We have developed coXpress as a means of identifying groups of genes that are differentially co-expressed. The utility of ... Here we describe coXpress, an R package that allows researchers to identify groups of genes that are differentially co- ... However, these methods may miss groups of genes which form differential co-expression patterns under different subsets of ... Our software identifies several groups of genes that are highly correlated under one set of biologically related experiments, ...
Witte cracked the code for CML in the mid-1980s, identifying how the BCR-Abl gene contributed to CML. His lab identified ... Witte discovered a previously unknown gene, Brutons tyrosine kinase (Btk), while studying X-linked agammaglobulinemia (XLA), ...
Hypereosinophilic syndrome and/or chronic eosinophilic leukaemia with FIP1L1-platelet-derived growth factor receptor alpha gene ... Philadelphia chromosome (BCR-ABL translocation)-positive acute lymphoblastic leukaemia. * Philadelphia chromosome (BCR-ABL ... Myelodysplastic / myeloproliferative diseases associated with platelet-derived growth factor receptor gene re-arrangements ...
Gene context of Leukemia, Myeloid, Chronic. *Bcr-Abl is a chimeric oncoprotein that is strongly implicated in acute ... wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary ... The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have ... Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. Mitani, ...
ABL Control Gene Standards, BCR-ABL Mbcr Fusion Gene Standards, Primers and Probe Mix ABL, Primers and Probe Mix BCR-ABL Mbcr ... BCR-ABL Mbcr fusion gene transcript.. ABL control gene transcript.. Accurate detection of BCR-ABL Mbcr standards.. Reliable ... Reliable detection of ABL plasmid standards.. BCR-ABL Mbcr fusion gene transcript.. ABL control gene transcript.. ... BCR-ABL Mbcr fusion gene transcript.. BCR-ABL Mbcr fusion gene transcript. ...
... abl-derived protein P90A [Abelson mouse leukemia virus Ab-MLV,strain P90A, Genomic, 400 nt]./gene="abl-derived protein P90A, ... It has two readingframes and long terminal repeats./gene="oncogene v-abl"/codon_start=1/protein_id="CAA24781.1"/db_xref="GI: ... It has two readingframes and long terminal repeats./gene="oncogene v-abl"/codon_start=1/product="hypotheticl protein"/protein_ ... abl gene./codon_start=1/protein_id="CAB56205.1"/db_xref="GI:5912561"/db_xref="UniProtKB/TrEMBL:Q76R65"\/db_xref="taxon:11788" 1 ...
Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 1997;387:516-19. ... The ATM gene in human lymphoid malignancies. The ATM gene is assigned to 11q22.3.5 Chromosome loss at 11q22-23 is a frequent ... The importance of inactivation of the ATM gene in T-PLL is now clear.34, 36, 37 How frequently inactivation of this gene occurs ... THE ATM GENE IN HUMAN LYMPHOMA. Further support for the proposal that inactivation of the ATM gene may be of importance to the ...
  • Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). (wikipedia.org)
  • Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease. (nih.gov)
  • Abetalipoproteinemia is caused by mutations in the MTTP gene, which provides instructions for making a protein called microsomal triglyceride transfer protein. (medlineplus.gov)
  • Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function and unable to help in the formation of beta-lipoproteins. (medlineplus.gov)
  • which means both copies of the gene in each cell have mutations. (medlineplus.gov)
  • CHMFL-074 shows better inhibitory activity than Imatinib against indigenous BCR-ABL kinase and several mutations such as for example E255K, F317L, F317I, M351T, Q252H,Y253F and H369P. (molecularcircuit.com)
  • ALL cancers have lots of additional changes, the so-called 'passenger' mutations, that may contribute to the cancer, but are not the main genes. (cancerquest.org)
  • Table 1 provides a summary of cancers and gene mutations. (frontiersin.org)
  • Frequent inactivating mutations of the ATM gene have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL), B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma (MCL). (bmj.com)
  • The presence of inactivating mutations, together with the deletion of the normal copy of the ATM gene in some patients with T-PLL, B-CLL, and MCL, establishes somatic inactivation of the ATM gene in the pathogenesis of lymphoid malignancies, and strongly suggests that ATM functions as a tumour suppressor. (bmj.com)
  • We now demonstrate that null mutations of Drosophila Dab result in phenotypes that mimic Abl mutant phenotypes, both in axon guidance and epithelial morphogenesis. (biologists.com)
  • The Dab mutant interacts genetically with mutations in Abl , and with mutations in the Abl accessory factors trio and enabled ( ena ). (biologists.com)
  • The molecular causes of the majority of MPN cases have been identified - mutations in the genes JAK2 and ABL are found in nearly all patients with polycythemia vera and chronic myeloid leukemia, respectively. (ucsfhealth.org)
  • The gene view histogram is a graphical view of mutations across ABL1_ENST00000318560. (sanger.ac.uk)
  • These mutations are displayed at the amino acid level across the full length of the gene by default. (sanger.ac.uk)
  • Mutations of the Janus kinase 2 ( JAK2 ) gene are responsible for polycythemia vera and a high proportion of cases of essential thrombocythemia and primary myelofibrosis. (msdmanuals.com)
  • CML is triggered by a chromosomal abnormality (an error during cell growth) in which the ABL gene is mistakenly joined to the BCR gene, forming a mutated BCR-ABL "fusion gene. (cancercare.org)
  • Taken as a pill once or twice daily, TKIs target the protein made by the mutated BCR-ABL fusion gene. (cancercare.org)
  • Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib. (wikipedia.org)
  • Dialogue Imatinib, the initial launched focus on therapy, which potently inhibits BCR-ABL, c-KIT and PDGFRs provides achieved remarkable achievement in the center [5]. (molecularcircuit.com)
  • Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. (lu.se)
  • One of the best-characterized forms of HES is the one associated with FIP1L1-PDGFRA gene rearrangement, which was recently demonstrated as responsive to treatment with the small molecule kinase inhibitor drug, imatinib mesylate. (wjgnet.com)
  • In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. (wikipedia.org)
  • Rowley had identified the first "translocation" in cancer, providing clear evidence that the cause of CML could be related to the fact that by moving from one chromosome to another, the aberrant segment of chromosome 22 was no longer sitting next to genes that controlled its behavior. (laskerfoundation.org)
  • This chromosome results from the faulty fusion of two genes - Bcr from chromosome 22, and Abl on chromosome 9. (rxwiki.com)
  • Chronic Myeloid Leukemia (CML) is associated with translocation between chromosome 9 & chromosome 22, t(9;22)(q34;q11.2) and with the formation of BCR-ABL fusion gene. (who.int)
  • This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. (wikipedia.org)
  • The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. (wikipedia.org)
  • This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. (nih.gov)
  • HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)
  • The ATM gene encodes a large protein that belongs to a family of kinases possessing a highly conserved C-terminal kinase domain related to the phosphatidylinositol 3-kinase domain. (bmj.com)
  • 4 - 7 The ATM gene encodes a nuclear phosphoprotein of approximately 350 kDa (3056 amino acids) and is ubiquitously expressed. (bmj.com)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus. (wikipedia.org)
  • 335\333\AAB20358.1\Abelson murine leukemia virus\abl-derived protein P90A [Abelson mouse leukemia virus Ab-MLV,strain P90A, Genomic, 400 nt]. (or.jp)
  • 3903\2757\CAA24781.1\Abelson murine leukemia virus\Abelson murine leukemia virus genome with v-abl oncogene. (or.jp)
  • 4724\492\CAA24782.1\Abelson murine leukemia virus\Abelson murine leukemia virus genome with v-abl oncogene. (or.jp)
  • 3662\492\CAB56205.1\Abelson murine leukemia virus\Abelson (P160) murine leukemia virus (Ab-MLV) abl gene. (or.jp)
  • The Abelson non-receptor tyrosine kinase (Abl) family has been implicated in a broad range of biological processes, such as oncogenesis, cell growth, adhesion, migration, neurite extension and growth cone motility (for a review, see Pendergast, 2002 ). (biologists.com)
  • Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)
  • 4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.com)
  • Genetic epistasis tests show that Dab functions upstream of Abl and ena , and, consistent with this, we show that Dab is required for the subcellular localization of these two proteins. (biologists.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • If the disease is discovered early, it almost always responds to the drug Gleevec, which puts the brakes on Bcr-Abl activity. (news-medical.net)
  • 3 , 4 The ATM gene is located at 11q22-23, spans 184 kb of genomic DNA, and has 66 exons. (bmj.com)
  • Moreover, genome instability was attributed to impaired autophagy and several autophagy genes with tumor suppressor functions (e.g. (hindawi.com)
  • We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. (lu.se)
  • The ABL1 gene is expressed as either a 6- or a 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11. (wikipedia.org)
  • One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. (nih.gov)
  • Specific primers and probe mixes and standard serial dilutions of control and fusion DNA are provided for the quantification of the BCR-ABL1 Mbcr genes and the ABL control gene according to Europe Against Cancer (EAC) recommendations (see figures BCR-ABL Mbcr fusion gene transcript. BCR-ABL Mbcr fusion gene transcript. "> BCR-ABL Mbcr fusion gene transcript and ABL control gene transcript. ABL control gene transcript. "> ABL control gene transcript ). (qiagen.com)
  • BCR-ABL Mbcr fusion gene transcript. (qiagen.com)
  • Through extensive chemical and genetic tests conducted in collaboration with an international group of researchers, Perrotti determined that Bcr-Abl stimulates a protein called SET, which, in turn, inhibits the phosphatase PP2A. (news-medical.net)
  • Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL) located on chromosome 9. (wikipedia.org)
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. (lu.se)
  • This is in contrast with tumor suppressor genes which must BOTH be defective to lead to abnormal cell division. (cancerquest.org)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
  • The study identified 2 genes known to contribute to tumor progression and 8 known to be present in tumor cells but which have unknown functions. (frontiersin.org)
  • In conclusion, the data shown here demonstrated that CHMFL-074 was impressive against both unchanged CML cell lines and BCR-ABL positive individual major hematopoietic cells. (molecularcircuit.com)
  • Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. (scielo.br)
  • Of the 30,000 or so genes that are currently thought to exist in the human genome , there is a small subset that seems to be particularly important in the prevention, development, and progression of cancer. (cancerquest.org)
  • Genes to Cells. (wikipedia.org)
  • They carry genes, which tell your cells what to do. (webmd.com)
  • It carries a new gene called bcr-abl, which sets off a process that creates abnormal white blood cells. (webmd.com)
  • They kill off CML blood cells by blocking the protein made by the abnormal gene bcr-abl. (webmd.com)
  • Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
  • Bcr-Abl permanently "turns on" cell growth signals that are normally held in check by molecules called phosphatases, and the result is the uncontrolled production of white blood cells, the hallmark of CML. (news-medical.net)
  • These ATG genes are highly conserved in mammalian cells, allowing to study their functions also in higher eukaryotes [ 1 - 4 ]. (hindawi.com)
  • The BCR-ABL gene leads to the production of an abnormal protein that fuels the growth of leukemia cells. (cancercare.org)
  • Ponatinib is often used to treat CML that has a specific additional alteration in the BCR-ABL gene known as T315I, which makes CML cells resistant to treatment with other TKIs. (cancercare.org)
  • Our scientists pursue every aspect of cancer research-from exploring the biology of genes and cells, to developing immune-based treatments, uncovering the causes of metastasis, and more. (mskcc.org)
  • There are three methods for making chronic myelogenous leukemia (CML) mouse models: xenotransplantation of primary Ph-positive CML cells into immunodeficient mice, BCR/ABL-expressing transgenic mice, and BCR/ABL retroviral bone marrow transduction and transplantation. (eurekaselect.com)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • Fluorescence in-situ hybridization (FISH) showed BCR-ABL fusion signals pattern in 100% nucleated cells analyzed. (who.int)
  • The t(9;22) translocation results in the head-to-tail fusion of the BCR and ABL1 genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. (wikipedia.org)
  • This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. (wikipedia.org)
  • BCR gene fused ABL kinase may be the critical traveling pressure for the Philadelphia Chromosome positive (Ph+) Chronic Myeloid Leukemia (CML) and continues to be extensively explored like a medication target. (molecularcircuit.com)
  • No monocytosis, EOSINOPHILIA, or basophilia is present, nor is there a PHILADELPHIA CHROMOSOME or bcr-abl fusion gene (GENES, ABL). (bvsalud.org)
  • Orthologous to human ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase). (nih.gov)
  • controlled for UV-induced mutational load by comparing mutated genes-of-interest against a baseline level of intronic mutation. (frontiersin.org)
  • The association between mutation of the ATM gene and a high incidence of lymphoid malignancy in patients with AT, together with the development of lymphoma in Atm deficient mice, supports the proposal that inactivation of the ATM gene may be of importance in the pathogenesis of sporadic lymphoid malignancy. (bmj.com)
  • Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)
  • Interestingly, when leukemic mice treated with forskolin stopped getting the treatment, some died of leukemia and others showed evidence of Bcr-Abl activity. (news-medical.net)
  • To date, The model mice using the BCR/ABL retroviral bone marrow transduction and transplantation method has provided the most valuable knowledge compared with the other two methods. (eurekaselect.com)
  • The translocation creates a new, fused gene (called BCR-ABL), that produces a cancer-causing enzyme called Bcr-Abl. (news-medical.net)
  • Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration. (nih.gov)
  • We therefore infer that Dab is a bona fide component of the core Abl signaling pathway in Drosophila . (biologists.com)
  • To ensure highest sensitivity, the ipsogen BCR-ABL1 Mbcr Kit has been optimized to detect BCR-ABL Mbcr p210 b2a2 or b3a2 transcripts and the ABL control gene using prediluted plasmid standards and primers and probe mixes (see figures Accurate detection of BCR-ABL Mbcr standards. BCR-ABL Mbcr standards (F1–F5): 10 1 , 10 2 , 10 3 , 10 5 , and 10 6 copies/5 µl. "> Accurate detection of BCR-ABL Mbcr standards and Reliable detection of ABL plasmid standards. ABL standards (C1–C3): 10 3 ,10 4 , and 10 5 copies/5 µl. "> Reliable detection of ABL plasmid standards ). (qiagen.com)
  • The ipsogen BCR-ABL1 Mbcr Kit is a ready-to-use kit for the detection of BCR-ABL Mbcr p210 b2a2 or b3a2 fusion gene transcripts using real-time PCR. (qiagen.com)
  • The ipsogen BCR-ABL1 Mbcr Kit provides 5 standard dilutions for Mbcr and 3 standard dilutions for ABL. (qiagen.com)
  • Using the ipsogen BCR-ABL1 Mbcr Kit allows detection and quantification of BCR-ABL Mbcr p210 b2a2 or b3a2 fusion gene and ABL transcripts. (qiagen.com)
  • The ipsogen BCR-ABL1 Mbcr Kit enables sensitive and reliable detection and quantification of BCR-ABL Mbcr p210 b2a2 or b3a2 transcripts, relative to ABL control gene expression, for research use only. (qiagen.com)
  • Mouse insertional mutagenesis experiments support the designation of ABL1_ENST00000318560 as a cancer causing gene. (sanger.ac.uk)
  • A diagram showing the major cancer genes for some cancers. (cancerquest.org)
  • identified 189 frequently mutated genes associated with these cancers, most of which were not previously known. (frontiersin.org)
  • Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. (lu.se)
  • IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically nonoverlapping with IM-induced apoptosis. (lu.se)
  • Immune escape is mainly caused by histocompatibility complex (MHC) class I, abnormal antigen signaling mechanism, immunosuppressive components (such as HLA-G), Fas and its ligands to activate apoptosis and overexpression of other immunosuppressive molecules, such as lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) ( Steven and Seliger, 2018 ). (techscience.com)
  • TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
  • In 71 out of 83 cases the typical interphase FISH signal patterns of BCR/ABL gene rearrangements was identified - one red signal, one green signal and two fusion signals (1R1G2F). (rrml.ro)
  • There is no longer a need for signals to activate these genes. (cancerquest.org)
  • Many of these genes are responsible for providing the positive signals that lead to cell division. (cancerquest.org)
  • The AT locus was mapped to the chromosomal region 11q22-23 using genetic linkage analysis in the late 1980s and the causative gene was identified by positional cloning several years later. (bmj.com)
  • The various other important level of resistance mechanism is because of the amplification from the BCR-ABL gene [10]. (molecularcircuit.com)
  • Side arrows in panels a and c indicate the position of the 3 kb IPCR bands resulting from the amplification of the intact ABL gene. (biomedcentral.com)
  • The kit is based on the amplification and detection of specific BCR-ABL Mbcr p210 b2a2 or b3a2 transcripts, relative to ABL control gene expression, in total RNA. (qiagen.com)
  • The fusion protein - BCR-ABL - is known as a tyrosine kinase. (rxwiki.com)
  • There is some evidence that the expression of Abl is regulated by the microRNA miR-203. (wikipedia.org)
  • We found a significantly lower expression of key autophagy- (ATG-) related genes in primary AML as compared to healthy granulocytes, an increased autophagic activity during all- trans retinoic acid- (ATRA-) induced neutrophil differentiation, and an impaired AML differentiation upon inhibition of ATG3, ATG4D, and ATG5. (hindawi.com)
  • Low PU.1 expression in AML may account for low ATG gene expression in this disease. (hindawi.com)
  • Traditional methods of analysing gene expression data often include a statistical test to find differentially expressed genes, or use of a clustering algorithm to find groups of genes that behave similarly across a dataset. (biomedcentral.com)
  • However, these methods may miss groups of genes which form differential co-expression patterns under different subsets of experimental conditions. (biomedcentral.com)
  • coXpress can be used to find groups of genes that display differential co-expression patterns in microarray datasets. (biomedcentral.com)
  • Microarrays have become a standard tool for the exploration of global gene expression changes at the cellular level [ 1 ]. (biomedcentral.com)
  • However, genes which show highly correlated patterns of expression in one biological state, but not in another, may not be highly correlated across the entire dataset, and therefore would not be associated with one another if a clustering algorithm is used. (biomedcentral.com)
  • Variation may exist in the expression of a gene in different groups of individuals due to the presence of sub-populations, and this may lead to that gene being grouped incorrectly. (biomedcentral.com)
  • Li [ 9 ] describes a method whereby genes whose expression is associated with differential co-expression patterns in other pairs of genes may be discovered, and Lai et al [ 10 ] describe a conceptually similar method whereby pairs of genes that display differential co-expression patterns between the normal and cancerous state may be discovered. (biomedcentral.com)
  • Other approaches have centred on the construction of large gene co-expression networks. (biomedcentral.com)
  • The kit provides reagents optimized for reliable and sensitive detection and quantification of BCR-ABL Mbcr b2a2 or b3a2 transcripts, relative to ABL control gene expression, in total RNA. (qiagen.com)
  • In the study, we used weighted gene co-expression network analysis to construct a co-expression network to screen out highly prognostic immune-related genes. (techscience.com)
  • Combined with the up-regulation of the expression of antioxidant genes (skn-1, sod-1, sod-3, mev-1, and gst-4), HME may function as an antioxidant in nematodes, which may be closely related to its phenolic compounds. (bvsalud.org)
  • Our data have provided evidence for a comparable prediction of clinical outcome in CMF-treated breast cancer patients using conventional clinical variables and gene expression based markers. (lu.se)
  • Prognostic models based on immune-related genes help to improve the prognosis prediction and clinical treatment of breast cancer patients. (techscience.com)
  • Subsequently, the prognostic immune-related gene signature was successfully constructed from highly immune-related genes through COX regression and LASSO COX analysis. (techscience.com)
  • Nowell, a tumor biologist in the pathology department at the University of Pennsylvania School of Medicine, was interested in the relationship between cancer and alterations in genes (although he had no proof there was one). (laskerfoundation.org)
  • The Cables1 Gene in Glucocorticoid Regulation of Pituitary Corticotrope Growth and Cushing Disease. (nih.gov)
  • Regulation of MT dynamics via direct binding of an Abl family kinase. (nih.gov)
  • The genes that have been identified to date have been categorized into two broad categories, depending on their normal functions in the cell. (cancerquest.org)
  • Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
  • We have two copies of each gene and for oncogenes, a single defective copy is enough to cause a cell to divide. (cancerquest.org)
  • As stated in the introduction to this section, the defective versions of these genes, known as oncogenes, can cause a cell to divide in an unregulated manner. (cancerquest.org)
  • Despite the differences in their normal roles, these genes all contribute to unregulated cell division if they are present in a mutant (oncogenic) form. (cancerquest.org)
  • But starting treatment again with forskolin - even weeks after initial treatment had stopped - blocked Bcr-Abl activity and reinstated normal cell functioning. (news-medical.net)
  • Abl is an essential regulator of cell migration and morphogenesis in both vertebrates and invertebrates. (biologists.com)
  • This article reviews the history of BCR/ABL-expressing CML mouse models and the recent findings in the transgenic mice with the CML-phenotype. (eurekaselect.com)
  • Mechanisms of Cables 1 gene inactivation in human ovarian cancer development. (nih.gov)
  • The Cables gene on chromosome 18q is silenced by promoter hypermethylation and allelic loss in human colorectal cancer. (nih.gov)
  • The larger the gene name, the more frequently that gene is defective in that cancer type. (cancerquest.org)
  • These genes have been found to be either malfunctioning or non-functioning in many different kinds of cancer. (cancerquest.org)
  • The immune-related gene signature effectively predicts the survival and immune infiltration of breast cancer patients and is expected to provide more effective immunotherapy targets for the prognosis prediction of breast cancer. (techscience.com)
  • This is NOT a known cancer gene. (sanger.ac.uk)
  • It is not found in the Cancer Gene Census . (sanger.ac.uk)
  • This gene does not have a cancer hallmark. (sanger.ac.uk)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. (nih.gov)
  • As an example TP 53 refers to the gene and p53 refers to the protein. (cancerquest.org)
  • in 1993, Dr. Witte discovered a previously unknown gene, Bruton's tyrosine kinase (Btk), while studying X-linked agammaglobulinemia (XLA), an often fatal genetic disease that weakens the immune system. (aamc.org)
  • We tried several gene selection strategies, and built classifiers using the resulting cDNA microarray gene lists. (lu.se)