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.
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.
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.
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)

susceptible to siRNA mediated degradation than medium and high abundant transcripts. Surprisingly, we found that co administration of BCRABL siRNA with imatinib or nilotinib resulted in enhanced inhibition Afatinib 439081-18-2 of cell growth and BCR ABL gene expression in 32Dp210 … Continue reading →. ...
References for Abcams Recombinant human ABL2 protein (ab51259). Please let us know if you have used this product in your publication
Description. Image from ?Farthest North. Being the record of a voyage of exploration of the ship ?Fram,? 1893-96, and of a fifteen months? sleigh journey by Dr. Nansen and Lieut. Johansen ? With an appendix by Otto Sverdrup, etc. [With plates, including portraits.]?, 002603734 Author: Nansen, Fridtjof Volume: 01 Page: 327 Year: 1897 Place: New York Publisher: Harper & Bros. View this image on Flickr View all the images from this book Following the link above will take you to the British Library?s integrated catalogue. You will be able to download a PDF of the book this image is taken from, as well as view the pages up close with the itemViewer?. Click on the related items? to search for the electronic version of this work ...
AMA : Bir BCR-ABL tirozin kinaz inhibit r olan imatinib in etkinli ine kar n baz hastalarda ilaca kar diren geli imi g zlenmektedir.. Diren geli imine neden olan en nemli mekanizma, ABL geninin tirozin kinaz ve ATP b lgelerindeki nokta mutasyonlar d r. Bu al ma ABL gen mutasyonlar n n taranmas nda denat re edici HPLC (dHPLC) y nteminin yerini ve nemini a klama amac yla yap lm t r ...
BCR-ABL is a mutation that is formed by the combination of two genes, known as BCR and ABL. Its sometimes called a fusion gene. The BCR gene is normally on chromosome number 22. The ABL gene is normally on chromosome number 9. The BCR-ABL mutation happens when pieces of BCR and ABL genes break off and switch places ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
c-Abl antibody [ABL-148] (ABL proto-oncogene 1, non-receptor tyrosine kinase) for FACS, ICC/IF, IP, WB. Anti-c-Abl mAb (GTX10528) is tested in Human, Mouse, Monkey, Rat, Bovine samples. 100% Ab-Assurance.
JBC Papers in Press. Published on January 11, 2013 as Manuscript R The latest version is at STRUCTURE AND DYNAMIC REGULATION OF ABL KINASES*
Business Standard News: Director Report : ABL Bio-Technologies Director Report, ABL Bio-Technologies updates and more at Business Standard news.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
The (9;22) translocation which produces the Philadelphia (Ph1) chromosome activates the abl oncogene from chromosome 9 by recombination with the bcr gene from chromosome 22. This fusion gene is transcribed into a new 8.5-kilobase chimeric mRNA which is translated into a novel Mr 210,000 fusion protein which has a protein tyrosine kinase activity that is greatly increased in comparison to the activity of the normal abl protein. Studies from this laboratory and others have shown that virtually all patients with chronic myelogenous leukemia have this new bcr/abl fusion gene. In contrast to these findings in chronic myelogenous leukemia, a small number of patients with Ph1(+) acute lymphoblastic leukemia (ALL) have been studied and were found to lack the bcr/abl fusion gene [bcr(-)], but to have a new activation of abl, by recombination with an as yet undetermined region on chromosome 22. In this study, nine adults with Ph1(+)-ALL have been examined for evidence of a bcr/abl fusion gene. Of the nine ...
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the ...
The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAFV600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAFV600E/ERK signaling and Abl kinases. We demonstrate that BRAFV600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation by Src family kinases. Importantly, Abl/Arg activation downstream of BRAFV600E has functional and biological significance, driving proliferation, invasion, as well as switch in epithelial-mesenchymal-transition transcription factor expression, which is known to be critical for melanoma cells to shift between differentiated and
The activation loop controls catalytic activity in most kinases by switching between different states in a phosphorylation-dependent manner (12). In fully active kinases, the loop is stabilized in an open conformation by phosphorylation on serine, threonine or tyrosine residues within the loop, and in this conformation a β-strand in the loop provides a platform for substrate binding. Three highly conserved residues in the NH2-terminal region of this loop (an Asp-Phe-Gly motif, residues 381 to 383 in Abl) are thereby held in a conformation that is appropriate for metal ion ligation by the aspartic side chain. This active conformation of the loop is very similar in all known structures of active kinases. There is, however, great diversity in the conformations of this loop in inactive protein kinases, in which the loop often occludes substrate binding. Additionally, crankshaft-like displacements in the NH2-terminal region of the loop change the conformation of the Asp-Phe-Gly triad, thereby ...
We used specific antisera and immunohistochemical methods to investigate the subcellular localization and expression of Bcr, Abl, and Bcr-Abl proteins in leukemic cell lines and in fresh human leukemic and normal samples at various stages of myeloid differentiation. Earlier studies of the subcellula …
Funding designed to support pre-IND studies of the companys novel Abelson tyrosine kinase (c-Abl) inhibitors as a potential Parkinsons disease treatment
Summary of ABL1 (ABL, c-ABL, JTK7, p150) expression in human tissue. Cytoplasmic and nuclear expression at variable levels in all tissues.
ABL Europe is 100 % dedicated to viral vectors. ABL Europe has completed projects from process and analytical development using a variety of manufacturing technologies resulting in the delivery of over 100 DS lots & 200 DP of clinical trial materials (Phase 1 to 3).. ...
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Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examined the role of normal ABL1 in leukemias induced by oncogenic ABL1 kinases. BCR-ABL1-Abl1(-/-) cells generated highly aggressive chronic myeloid leukemia (CML)-blast phase-like disease in mice compared with less malignant CML-chronic phase-like disease from BCR-ABL1-Abl1(+/+) cells. Additionally, loss of ABL1 stimulated proliferation and expansion of BCR-ABL1 murine leukemia stem cells, arrested myeloid differentiation, inhibited genotoxic stress-induced apoptosis, and facilitated accumulation of chromosomal aberrations. Conversely, allosteric stimulation of ABL1 kinase activity enhanced the antileukemia effect of ABL1 tyrosine kinase inhibitors (imatinib and ponatinib) in human and murine leukemias expressing BCR-ABL1, TEL-ABL1, and NUP214-ABL1.
The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185ALL-ABL. Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210BCR-ABL but not P185ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the ...
Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. This, in turn, allows the cell to become cancerous. 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. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABLs influence on the cell cycle. Second generation BCR-ABL ...
The ABL proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Mutations in the ABL gene are associated with chronic myelogenous leukemia (CML), where it is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. ABL exon 4 primer set have the function to enrich mutation type of ABL gene and allows to detect target codons M244 on DNA samples.. ...
The ABL proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Mutations in the ABL gene are associated with chronic myelogenous leukemia (CML), where it is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. ABL exon 6 primer set have the function to enrich mutation type of ABL gene and allows to detect target codons T315 on DNA samples.. ...
TY - JOUR. T1 - Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1. AU - Tomita, Osamu. AU - Iijima, Kazutoshi. AU - Ishibashi, Takeshi. AU - Osumi, Tomoo. AU - Kobayashi, Kenichiro. AU - Okita, Hajime. AU - Saito, Masahiro. AU - Mori, Tetsuya. AU - Shimizu, Toshiaki. AU - Kiyokawa, Nobutaka. PY - 2014/3/1. Y1 - 2014/3/1. N2 - We introduced SNX2-ABL1, a novel ABL1-related chimeric transcript lacks SH3 and SH2 domains, into murine Ba/F3 cells and compared their function with that of BCR-ABL1. After the expression of SNX2-ABL1 proteins, Ba/F3 cells acquired an ability to proliferate in an IL-3-independent manner. Upon treatment with both imatinib and dasatinib, BCR-ABL1-expressing Ba/F3 cells underwent rapid apoptosis, whereas SNX2-ABL1-expressing Ba/F3 cells showed poorer sensitivity toward these TKIs and could proliferate in the presence of a low dose of dasatinib. Therefore, other TKIs with a more selective effect against this chimeric kinase should be ...
The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR (MIM:151410) and ABL1 genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11. [provided by RefSeq, Jul 2008 ...
The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR (MIM:151410) and ABL1 genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11. [provided by RefSeq, Jul 2008 ...
Dr. Liawaty Ho answered: CML: CML is associated with philadelphia chromosome that result in the abnormal bcr-abl fusion gene. This becomes the target of tr...
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摘 要:BCR/ABL融合蛋白是慢性粒细胞白血病(CML)的分子标志,具有高激酶活性,其在疾病发生、发展中扮演了极其重要的角色。伊马替尼(Imatinib)靶向抑制BCR-ABL,为CML慢性期的一线治疗药。BCR/ABL与Src家族激酶(Src-family kinases, SFK)之间也存在相互活化作用,通过激活众多信号通路,导致CML向急变期发展,并导致伊马替尼耐药。对有关BCR/ABL与SFK两者的相互作用机制及其生物学效应的研究进行总结 ...
Keywords: lentivirus, tumor control cell infections, mobile transduction Launch Cancers control cells (CSCs) lead to growth maintenance and repeat via healing level of resistance, angiogenesis, and intrusion [1-6]. The molecular systems mediating these protumorigenic results are of significant curiosity as id of story paths can offer story possibilities for targeted therapy advancement [5-6]. To elucidate CSC particular indicators and the biologies they control, paths may end up being modulated via gene knockdown and overexpression. While CSC transfection may end up being challenging, infections can offer an effective system through which Palmitoyl Pentapeptide to exhibit particular genetics or brief hairpin sequences in CSCs. One technique through which CSCs can end up being transduced is certainly through the make use of of lentivirus, a known member of a family members of enveloped infections which may infect mammalian cells [7-9]. As lentivirus is certainly able of infecting and ...
Supplementary Materials Shape?S1 Vacuolar sorting efficiency. the predominant existence of plant normal complicated fucosylated and xylosylated GnGnXF constructions on sec\Ab while vac\Ab muscles carried primarily oligomannosidic (Guy 7\9) next to GnGnXF forms. Paucimannosidic glycans Rabbit Polyclonal to ABCD1 (frequently assigned as normal vacuolar) werent recognized. Confocal microscopy evaluation using RFP fusions demonstrated that sec\Ab\RFP localized in the apoplast while vac\Abs\RFP had been exclusively recognized in the central vacuole. The info claim that vac\Abs reached the vacuole by two different pathways: immediate transport through the ER bypassing the Golgi (Ab substances containing Man constructions) and trafficking through the Golgi (for Ab substances containing complicated N\glycans). Importantly, vac\Abs had been properly constructed and functionally energetic. Collectively, we show that the central vacuole is an appropriate compartment for the efficient production of Abs ...
A2M single QLD A2ML1 single QLD A2ML1 single QLD AAAS single QLD AAAS single QLD AARS single QLD AARS2 single QLD AARS2 single QLD AASS single QLD ABAT single QLD ABAT single QLD ABAT single QLD ABCA1 single QLD ABCA1 single QLD ABCA1 single QLD ABCA12 single QLD ABCA12 single QLD ABCA3 single QLD ABCA4 single QLD ABCA4 single QLD ABCB1 single QLD ABCB11 single QLD ABCB4 single QLD ABCB6 single QLD ABCB6 single QLD ABCB7 single QLD ABCC11 single QLD ABCC3 single QLD ABCC6 single QLD ABCC6 single QLD ABCC8 single QLD ABCC8 single QLD ABCC8 single QLD ABCC9 single QLD ABCC9 single QLD ABCC9 single QLD ABCD1 single QLD ABCD1 single QLD ABCD1 single QLD ABCD1 single QLD ABCD1 single QLD ABCD2 single QLD ABCD3 single QLD ABCD4 single QLD ABCD4 single QLD ABCG2 single QLD ABCG5 single QLD ABCG5 single QLD ABCG8 single QLD ABCG8 single QLD ABHD12 single QLD ABHD12 single QLD ABL1 single QLD ABL1 single QLD ABL1 single QLD ABL1 tyrosine kinase domain mutation analysis Single CHRISTCHURCH ABL2 single QLD ...
Mouse monoclonal antibody raised against a partial recombinant ABL2. ABL2 (AAH65912, 743 a.a. ~ 842 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa. (H00000027-M05) - Products - Abnova
Regulatory News: Transgene SA (Paris:TNG) (Euronext: TNG) a company specializing in immunotherapies, and ABL, Inc., a contract research and manufactur
Expression of ABL2 (ABLL, ARG) in oral mucosa tissue. Antibody staining with HPA001866, HPA072754 and CAB017106 in immunohistochemistry.
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www.sciencesignaling.org/cgi/content/full/9/413/ra12/DC1. Fig. S1. ABL family protein abundance is increased in breast cancer cells with enhanced bone metastatic activity, and ABL1/ABL2 depletion does not affect proliferation in vitro.. Fig. S2. ABL kinases promote breast cancer cell invasion.. Fig. S3. Depletion of ABL kinases does not inhibit metastasis of 4175 breast cancer cells, which show tropism to the lung.. Fig. S4. Treatment of breast cancer cells with imatinib but not GNF5 promotes ERK activation.. Fig. S5. CXCL12- and IGF-1-mediated survival pathways are independent of ABL kinases.. Fig. S6. Depletion of ABL kinases in SKBR3 breast cancer cells decreases tumor-induced osteoclast activation.. Fig. S7. IL-6 affects RANKL and OPG expression in osteoblasts.. Fig. S8. Quality control and global statistics of RNAseq analysis for transcriptome comparison of control versus ABL1/ABL2 knockdown breast cancer cells.. Fig. S9. ABL kinases increase TAZ protein abundance and STAT5 ...
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the ...
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the ...
The t(9;22)(q34;q11) chromosomal translocation is the most frequent cytogenetic abnormality found in human leukemias where it can be detected in ∼95% of patients with chronic myelogenous leukemia (CML) and in 30% to 40% of pre-B and acute lymphoblastic leukemia (1-3). This translocation results in the fusion of the BCR and ABL genes, leading to the expression of a BCR-ABL fusion protein with constitutively active ABL tyrosine kinase activity (1, 4). BCR-ABL-induced signaling is known to activate Ras-dependent signaling, phosphatidylinositol-3-kinase/Akt, and the Jak/STAT pathway (5). Additionally, BCR-ABL activates the transcription factor nuclear factor-κB (NF-κB) at least partly in a manner dependent on Ras (6). Suppression of NF-κB activation by expression of the so-called superrepressor form of IκBα blocked BCR-ABL-dependent xenograft tumor formation (6). Others (7) have also observed that NF-κB is activated by BCR-ABL in manner dependent on Ras. Furthermore, that study reported ...
The kinase domain of Abl lacking the amino acids in the C terminus is unable to bind myr pocket binders because it are not able to form the helix I thats a significant structural feature for that binding from the myristate moiety . Fig. b demonstrates the overall crystal construction of Abl kinase domain with GNF liganded towards the myr pocket and imatinib bound towards the ATP binding site. It need to be emphasized, that only these Abl kinase domain structures that consist of imatinib bound towards the ATP binding pocket are ready to get solved with the myr pocket binders.The requirement for ATP ligands inside the kind of ATP webpage directed inhibitors is vital to obtain stable with the Abl kinase domain for X ray crystallography . There may be really minor difference during the ATP binding web page also as amongst the relative orientations the N and terminal C lobe on the Abl kinase domain when comparing the Abl imatinib complicated using the Abl imatinib GNF or Abl purmorphamine imatinib ...
The break on chromosome 9 involves a gene called Abl and the break on chromosome 22 involves a gene called Bcr. The Bcr and Abl genes combine to make the CML causing gene called the Bcr-Abl gene. There doesnt seem to be any rhyme or reason as to why this occurs; it just does. This Bcr-Abl gene produces a dysfunctional protein called BCR-ABL tyrosine kinase; this leads to the abnormal regulation of cell growth and survival and is responsible for CML. Think of it as a faucet that is constantly in the on position. It is on and making immature white cells that are crowding out the good white cells as well as the red cells and platelets. ...
Free, official coding info for 2021 ICD-10-CM C92.11 - includes detailed rules, notes, synonyms, ICD-9-CM conversion, index and annotation crosswalks, DRG grouping and more.
Free, official coding info for 2018 ICD-10-CM C92.10 - includes detailed rules, notes, synonyms, ICD-9-CM conversion, index and annotation crosswalks, DRG grouping and more.
What does ABL stand for? Hop on to get the meaning of ABL. The Acronym /Abbreviation/Slang ABL means African Burkitt lymphoma. by AcronymAndSlang.com
TABLE-US-00006 TABLE 6 THI + 2 + 4 + 5 + 7 Composite (Meta-THc) OG- OG- OG- OG- OG- 3116 @ 3116 @ 3116 @ 3116 @ 3116 @ 50 100 1 μg/ml 5 μg/ml 25 μg/ml μg/ml μg/ml Abl(H396P)(h) 91 88 73 55 50 Abl(M351T)(h) 100 87 62 50 38 Abl(Q252H)(h) 89 86 58 45 44 Abl(h) 98 85 65 41 49 Abl(m) 99 87 60 47 43 Abl(T315I)(h) 100 91 79 65 52 Abl(Y253F)(h) 93 90 75 54 51 ACK1(h) 122 112 97 102 82 ALK(h) 76 38 17 16 26 ALK4(h) 96 95 85 68 48 Arg(h) 94 91 68 52 42 Arg(m) 100 99 94 73 50 ARK5(h) 100 97 82 64 75 Aurora-A(h) 92 79 40 41 27 Axl(h) 97 99 83 77 60 Blk(m) 95 102 71 49 54 Bmx(h) 91 94 84 77 43 BrSK1(h) 95 90 71 47 51 BrSK2(h) 91 82 77 70 63 BTK(h) 99 97 64 44 28 CaMKI(h) 95 84 46 28 48 CaMKII(r) 97 106 89 69 63 CaMKIIβ(h) 94 99 85 52 34 CaMKIIγ(h) 107 103 94 92 134 CaMKIIδ(h) 103 97 84 83 84 CaMKIV(h) 107 108 95 75 58 CaMKIδ(h) 91 93 92 75 80 CDK1/cyclinB(h) 99 101 91 71 58 CDK2/cyclinA(h) 105 106 92 83 63 CDK2/cyclinE(h) 99 103 75 60 42 CDK3/cyclinE(h) 108 100 96 79 45 CDK5/p25(h) 102 89 84 77 72 ...
ABL Europeu2019s (Strasbourg site) Certificate of GMP Compliance related to 2016 facility inspection for: Quality Control Testing ...
BioAssay record AID 632955 submitted by ChEMBL: Inhibition of Abl using DAIpYAAPFAKKK phosphopeptide as substrate by MALDI-MS analysis.
"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 ...
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 ...
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. ...
"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. ...
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. ...
Abl gene, Arachidonate 5-lipoxygenase, B-cell linker, BCAR1, BCR gene, Beta-2 adrenergic receptor, C-Met, CBLB, CD117, CD22, ... This gene is similar to the sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. Two ... In humans, the GRB2 protein is encoded by the GRB2 gene. The protein encoded by this gene binds receptors such as the epidermal ... "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". ...
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 ...
"Entrez Gene: RYBP RING1 and YY1 binding protein". CS1 maint: discouraged parameter (link) Zhu J, Shore SK (Dec 1996). "c-ABL ... RYBP has been shown to interact with: Abl gene, CBX2, Caspase 10, E2F2, E2F3, Mdm2, RING1, and YY1. ENSG00000163602 GRCh38: ... CS1 maint: discouraged parameter (link) Zhu J, Shore SK (Dec 1996). "c-ABL tyrosine kinase activity is regulated by association ... RING1 and YY1-binding protein is a protein that in humans is encoded by the RYBP gene. ...
Docking protein 2 is a protein that in humans is encoded by the DOK2 gene. The protein encoded by this gene is constitutively ... 2003). "Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization". J. Biol. Chem. 278 (32 ... "Entrez Gene: DOK2 docking protein 2, 56kDa". Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (2000). "The ... It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded ...
... 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 ...
"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 ( ...
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 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 ...
Resistance to BCR-ABL targeting drugs[edit]. In the case of Gleevec (Imatinib), which targets the BCR-ABL fusion gene in ... The mutated genes usually belong to classes of caretaker, gatekeeper, landscaper or several other genes. Mutation ultimately ... "Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency". ... The retinoblastoma gene was the first tumor suppressor gene to be cloned in 1986. ...
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 ...
Genes & Development. 5 (9): 1553-67. doi:10.1101/gad.5.9.1553. PMID 1884998. "Entrez Gene: CEBPD CCAAT/enhancer binding protein ... C/EBP), delta". Gery S, Tanosaki S, Hofmann WK, Koppel A, Koeffler HP (Feb 2005). "C/EBPdelta expression in a BCR-ABL-positive ... Function of CEBPD gene can be effectively examined by siRNA knockdown based on an independent validation. CEBPD has been shown ... CCAAT/enhancer-binding protein delta is a protein that in humans is encoded by the CEBPD gene. The protein encoded by this ...
Myeloid/lymphoid or mixed-lineage leukemia 4, also known as MLL4, is a human gene. This gene encodes a protein which contains ... "FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands". EMBO J. 16 (9): 2376-83. doi:10.1093/ ... This gene is ubiquitously expressed in adult tissues. It is also amplified in solid tumor cell lines, and may be involved in ... "Entrez Gene: MLL4 myeloid/lymphoid or mixed-lineage leukemia 4". CS1 maint: discouraged parameter (link) Bedford MT, Chan DC, ...
The Perth Heat defeated the Aces two games to one in the championship series, to win back-to-back ABL championships. Announced ... CS1 maint: discouraged parameter (link) Stephan, Gene (19 May 2011). "Heat to take on Asia's best teams". The West Australian. ... The Asia Series is held in November, which would otherwise create a conflict for the ABL champion team as the following season ... The season consists of six teams competing in a 45-game schedule followed by a three-round postseason to determine the ABL ...
... has been shown to interact with Abl gene, BCR gene, C-Raf, c-Kit, Insulin receptor, Insulin-like growth factor 1 receptor ... 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 ...
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 ...
... 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 US National Library of Medicine Medical Subject Headings (MeSH) Abelson+Leukemia+Virus at the US 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, ...
Genes Dev. 17 (20): 2508-2513. doi:10.1101/gad.1119403. PMC 218144. PMID 14561773. Kano S, Miyajima N, Fukuda S, Hatakeyama S ( ... July 2008). "Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2". Cancer Res ...
... has been shown to interact with: Abl gene, BZW1, CD2, PTPN12, PTPN18, and Wiskott-Aldrich syndrome protein. PAPA ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ... "Entrez Gene: PSTPIP1 proline-serine-threonine phosphatase interacting protein 1". Cong F, Spencer S, Côté JF, Wu Y, Tremblay ML ...
... 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 ...
The Abl gene expresses a membrane-associated protein, a tyrosine kinase, and the BCR-Abl transcript is also translated into a ... The ABL tyrosine kinase activity of BCR-Abl is elevated relative to wild-type ABL.[11] Since ABL activates a number of cell ... This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for ... Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. This gene ...
"Entrez Gene: SH3BP1 SH3-domain binding protein 1". Cicchetti P, Mayer BJ, Thiel G, Baltimore D (1992). "Identification of a ... protein that binds to the SH3 region of Abl and is similar to Bcr and GAP-rho". Science. 257 (5071): 803-6. doi:10.1126/science ... SH3 domain-binding protein 1 is a protein that in humans is encoded by the SH3BP1 gene. GRCh38: Ensembl release 89: ... 2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome ...
... gene. When these two chromosome fragments fuse the genes also fuse creating a new gene: "BCR-ABL". This fused gene encodes for ... Another example of an oncogene is the Bcr-Abl gene found on the Philadelphia chromosome, a piece of genetic material seen in ... which in turn regulate genes that mediate cell proliferation. Anticancer gene Oncogenomics Tumor suppressor gene Oncovirus ... An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at ...
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 ...
It is mainly used to treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[5] ...
RNA probes can be designed for any gene or any sequence within a gene for visualization of mRNA,[3][4][5] lncRNA[6][7][8] and ... A metaphase cell positive for the bcr/abl rearrangement (associated with chronic myelogenous leukemia) using FISH. The ... The technology has potential applications in cancer diagnosis,[14] neuroscience, gene expression analysis,[15] and companion ... An example is the detection of BCR/ABL translocations, where the secondary color indicates disease. This variation is often ...
"Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A ... Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ...
Abl gene,[58]. *Ataxia telangiectasia mutated,[58]. *BARD1,[59]. *BRCA1,[59][60][61][62] ... RAD51 is a eukaryotic gene. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of ... Many cancers have epigenetic deficiencies in various DNA repair genes (see Frequencies of epimutations in DNA repair genes in ... Gene ontology. Molecular function. • nucleotide binding. • DNA binding. • DNA-dependent ATPase activity. • recombinase activity ...
... they can be used to determine the tissue or cell type in which a given gene is required and to determine whether a gene is cell ... Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... The FLP gene can then be induced selectively, commonly using either the heat shock promoter or the GAL4/UAS system. The ... The flip recombinase (or FLP) is a gene from the commonly studied yeast Saccharomyces cerevisiae which recognizes "flip ...
... whereas most bacteria possess heat shock genes hslV and hslU, whose gene products are a multimeric protease arranged in a two- ... Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ... Sharp PM, Li WH (1987). "Ubiquitin genes as a paradigm of concerted evolution of tandem repeats". Journal of Molecular ...
"Gene. 570 (1): 25-35. doi:10.1016/J.GENE.2015.06.062. PMC 4519417. PMID 26119091.. CS1 maint: uses authors parameter (link). . ... "Charting the molecular network of the drug target Bcr-Abl". Proceedings of the National Academy of Sciences of the United ... Gene[edit]. The chromosomal location of the CASS4 gene is 20q13.31, with genomic coordinates of 20: 56411548-56459340 on the ... "Entrez Gene: Cas scaffolding protein family member 4".. *^ a b Tikhmyanova N, Little JL, Golemis EA (April 2010). "CAS proteins ...
Targets: t(9;22) BCR-ABL, t(12;21) ETV6-RUNX1 (TEL-AML1), Patient specific assays for immunoglobulin and T cell receptor genes ... Target: t(9;22) BCR-ABL Uses: MRD detection of the t(9;22) is considered standard of care for all patients with CML and is ... For example, the t(9;22) BCR-ABL translocation may occur over a large length of the chromosome which makes DNA-based testing ... The markers used for RNA-based testing are almost exclusively chromosomal translocations such as t(9;22) BCR-ABL, t(15;17) PML- ...
... is a rare chromosomal disorder resulting from deletion of genes from chromosome 11 that includes band 11q24.1 ... Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... which reveals the broken and deleted genes. The condition can also be diagnosed early in the prenatal stage if there are any ... which range from mild to moderate depending upon the number of the deletions of genes from the chromosome. Children with ...
In childhood ALL, this process begins at conception with the inheritance of some of these genes. These genes, in turn, increase ... Person with t(9,22) positive-ALL (30% of adult ALL cases) and other Bcr-abl-rearranged leukemias are more likely to have a poor ... Examples of this include the ETV6-RUNX1 fusion gene that combines two factors that promote blood cell development and the BCR- ... These rearrangements result in increased expression of blood cell development genes by promoting gene transcription and through ...
Strong evidence shows that the genes encoding the GluN2 subunits in vertebrates have undergone at least two rounds of gene ... Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ... Homozygous disruption of the gene for GluN2B in mice causes perinatal lethality, whereas disruption of the GluN2A gene produces ... and two GluN3 subunit encoding genes, and each gene may produce more than one splice variant. ...
... genes that control the growth rate of cells) and tumor suppressor genes (genes that help to prevent cancer), which gives cancer ... Upregulation of these genes can overcome the DNA damage and prevent the induction of apoptosis. Mutations in genes that produce ... With more copies of the gene, the drug can not prevent all expression of the gene and therefore the cell can restore its ... Another mechanism of resistance is gene amplification, a process in which multiple copies of a gene are produced by cancer ...
The BCR-ABL oncogene has been found to be involved in the development of cancer in humans. c-Myc is involved in the regulation ... The ATG genes control the autophagosome formation through ATG12-ATG5 and LC3-II (ATG8-II) complexes. ATG12 is conjugated to ... Unlike other cancer genes, which promote cancer by stimulating cell proliferation, BCL2 promoted cancer by stopping lymphoma ... ULK1 and ULK2 form a large complex with the mammalian homolog of an autophagy-related (Atg) gene product (mAtg13) and the ...
"PTK2 - Focal adhesion kinase 1 - Gallus gallus (Chicken) - PTK2 gene & protein" (英語). www.uniprot.org. 2021年9月5日閲覧。. ... "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". ... "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". 2008年10月28日閲覧。. ... "Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte ...
Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and ... Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML).[4] ... These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% ... or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to ...
Genetic disorders may be grouped into single-gene defects, multiple-gene disorders, or chromosomal defects. Single-gene defects ... Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... Genetic causes of birth defects include inheritance of abnormal genes from the mother or the father, as well as new mutations ... Most of these are single gene defects, usually heritable. Many affect the structure of body parts but some simply affect the ...
Bacteria usually acquire resistance to tetracycline from horizontal transfer of a gene that either encodes an efflux pump or a ... "Rapid generation of a tetracycline-inducible BCR-ABL defective retrovirus using a single autoregulatory retroviral cassette".. ...
Rasmussen N (2014). Gene Jockeys: Life Science and the rise of Biotech Enterprise. Baltimore: Johns Hopkins University Press. ... Discovery and development of Bcr-Abl tyrosine kinase inhibitors. *Discovery and development of antiandrogens ...
TEL/ABL. Llyfryddiaeth[golygu , golygu cod y dudalen]. *"Next-generation sequencing and molecular cytogenetic characterization ... "ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non-intestinal-type ...
Li-fraumeni syndrome»։ Genes & Cancer 2 (4): 475-84։ April 2011։ PMC 3135649։ PMID 21779515։ doi:10.1177/1947601911413466 , ... Այլ օրինակ en BCR-ABL-ի պաշարիչները, որոնք օգտագործվում են քրոնիկ միելոիդային լեյկեմիայի բուժման համար (CML)[16]: Ներկայումս ... Epigenetic changes of DNA repair genes in cancer»։ Journal of Molecular Cell Biology 3 (1): 51-8։ February 2011։ PMC 3030973։ ... Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?»։ Nature Reviews. Cancer 6 (2): 107-16 ...
... formira interakcije sa PDGFRB,[2][3] PLCG1,[4] Natrijum-vodonik antiporter 3 regulator 1,[5] Cbl gene,[6] CRK,[7][8] ... "Entrez Gene: PDGFRA platelet-derived growth factor receptor, alpha polypeptide". http://www.ncbi.nlm.nih.gov/sites/entrez?Db= ... gene&Cmd=ShowDetailView&TermToSearch=5156. *↑ Rupp, E; Siegbahn A; Rönnstrand L; Wernstedt C; Claesson-Welsh L; Heldin C H ( ...
Holoprosencephaly has been reported in some people with ring 18.[4] This is due to the deletion of the TGIF gene on the short ... Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... TCF4 - In 2007, deletions of or point mutations in this gene, which is located on 18q, were identified as the cause of Pitt- ... TSHZ1 - Point mutations and deletions of this gene, located on 18q, are linked with congenital aural atresia [6] Individuals ...
Gene locationEdit. The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair ... "Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation". Mol. Cell. Biol. 22 (12): ... Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[5] ... BRCA1 is a human tumor suppressor gene[7][8] (also known as a caretaker gene) and is responsible for repairing DNA.[9] ...
Entrez Gene: DDR2 discoidin domain receptor family, member 2".. *^ Ikeda, Kazuo; Wang Li-Hsien; Torres Richard; Zhao Hong; ... Lapsys NM; Layfield R; Baker E (1993). „Chromosomal location of the human transketolase gene.". Cytogenet. Cell Genet. 61 (4): ... Edelhoff S, Sweetser DA, Disteche CM (1995). „Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and ... Faraci E; Eck M; Gerstmayer B (2004). „An extracellular matrix-specific microarray allowed the identification of target genes ...
"Entrez Gene: C-src tyrosine kinase". http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=1445. pristupljeno ...
The Btk gene is located on the X chromosome (Xq21.3-q22).[5] At least 400 mutations of the BTK gene have been identified. ... Gene ontology. Molecular function. • metal ion binding. • nucleotide binding. • lipid binding. • receptor binding. • identical ... Human BTK genome location and BTK gene details page in the UCSC Genome Browser. ... Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's ...
The ABL folded in December 1962, just months into its second season. Steinbrenner and his partners lost significant money on ... He left day-to-day baseball matters in the hands of Gene Michael and other executives, and allowed promising farm-system ... Steinbrenner replaced McClendon with former Boston Celtics star Bill Sharman, and the Pipers won the ABL championship in 1961- ... ABL). Steinbrenner had hired John McClendon, who became the first African American coach in professional basketball and ...
Common examples of predictive biomarkers are genes such as ER, PR and HER2/neu in breast cancer, BCR-ABL fusion protein in ...
Talin-1 is a protein that in humans is encoded by the TLN1 gene.[5][6] Talin-1 is ubiquitously expressed, and is localized to ... Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (Feb 1996). "p210BCR/ABL induces formation of complexes containing focal ... Gene ontology. Molecular function. • structural constituent of cytoskeleton. • actin filament binding. • LIM domain binding. • ... Gilmore AP, Ohanian V, Spurr NK, Critchley DR (Aug 1995). "Localisation of the human gene encoding the cytoskeletal protein ...
... a few genes located in the pseudoautosomal regions of their X chromosomes have corresponding genes on their Y chromosome and ... Philadelphia chromosome t(9 ABL; 22 BCR). *Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) ... In mammals with more than one X chromosome, the genes on all but one X chromosome are not expressed; this is known as X ... As such, male cats with calico or tortoiseshell markings are a model organism for KS, because a color gene involved in cat ...
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 ...
IPR012849. Abl-interactor_HHR_dom. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. IPR000727. T_SNARE_dom. ... IPR012849. Abl-interactor_HHR_dom. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. IPR000727. T_SNARE_dom. ... Abl interactor 2Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a ... p>This subsection of the Names and taxonomy section indicates the name(s) of the gene(s) that code for the protein sequence(s ...
IPR012849. Abl-interactor_HHR_dom. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. IPR000727. T_SNARE_dom. ... IPR012849. Abl-interactor_HHR_dom. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. IPR000727. T_SNARE_dom. ... Abl-interactor 2aImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a ... p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of ...
BCR gene. References. *↑ "Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1".. .mw-parser-output cite. ... 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 ... This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in ... gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows ...
This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in ... previous symbol ABL) located on chromosome 9.[1] c-Abl is sometimes used to refer to the version of the gene found within the ... 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 ...
... c-Abl knockdown cells show a decrease in HDAC2 levels, while c-Abl overexpression increases them; (3) c-Abl inhibition reduces ... c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimers disease.. Gonzalez ... Our results support the participation of the c-Abl/HDAC2 signaling pathway in the epigenetic blockade of gene expression in AD ... Here, we described how the tyrosine kinase c-Abl increases HDAC2 levels, inducing transcriptional repression of synaptic genes ...
... in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of ... Fused transcript of abl and bcr genes in chronic myelogenous leukaemia Nature. 1985 Jun 13-19;315(6020):550-4. doi: 10.1038/ ... in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of ... of an 8-kilobase RNA specific to chronic myelogenous leukaemia shows it to be a fused transcript of the two genes. The fused ...
Abelson-related gene) ... Abl2 v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene) [Mus musculus]. Gene ... Abl2 v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene) [ Mus musculus (house mouse) ] Gene ID: 11352, ... Gene neighbors Overlapping genes and two nearest non-overlapping genes on either side ... v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene)provided by MGI. Primary source. MGI:MGI:87860 See ...
ABL protooncogene from chromosome 9, thereby leading to formation of alternative BCR-ABL fusion proteins p210BCR-ABL and p185 ... Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic ... Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic ... Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic ...
BCR/ABL gene explanation free. What is BCR/ABL gene? Meaning of BCR/ABL gene medical term. What does BCR/ABL gene mean? ... Looking for online definition of BCR/ABL gene in the Medical Dictionary? ... BCR/ABL gene. BCR/ABL gene (jēn) A fusion gene produced when a segment of the Abelson protooncogene, ABL, from chromosome 9, ... BCR/ABL gene , definition of BCR/ABL gene by Medical dictionary https://medical-dictionary.thefreedictionary.com/BCR%2fABL+gene ...
... was used to identify the most effective shRNA for inducing RNAi of the bcr/abl gene. ... Using Bioluminescent Reporter Genes to Optimize shRNA Target Sites for RNAi of the bcr/abl Gene. Natalie Betz. Promega ... Using-Bioluminescent-Reporter-Genes-to-Optimize-shRNA-Target-Sites-for-RNAi-of-the-bcr-abl-GenePDF. (. 118. KB. ). - English ... was used to identify the most effective shRNA for inducing RNAi of the bcr/abl gene. The seven shRNAs tested were generated ...
The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene ... The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene ... The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene ... The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene ...
The Novel Activation of ABL by Fusion to an ets-related Gene, TEL. Panos Papadopoulos, Susan A. Ridge, Catherine A. Boucher, ... We have identified a novel activation of ABL which involves a gene located on chromosome 12, designated TEL. Like BCR, TEL is ... The Novel Activation of ABL by Fusion to an ets-related Gene, TEL ... The Novel Activation of ABL by Fusion to an ets-related Gene, ... The Novel Activation of ABL by Fusion to an ets-related Gene, TEL ...
c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes. Ameer Ali Bohio, Aman ... c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes ... c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes ... c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes ...
Mutation in the BCR-ABL kinase domain might be a frequent mechanism of STI571 resistance in lymphoid disease. ... Different mutations within the kinase domain of BCR-ABL can be responsible for refractoriness of Ph+ leukaemia to STI571. ... BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a ... STI571, a competitive inhibitor at the ATP-binding site of BCR-ABL, has been shown to have high activity in this type of ...
Ikaros deletions in BCR-ABL-negative childhood acute lymphoblastic leukemia are associated with a distinct gene expression ... Gene ontology studies revealed an up-regulation of genes associated with cell adhesion, cytoskeletal regulation, and motility ... We report a specific gene expression signature of 735 up-regulated and 473 down-regulated genes in IKZF1 deleted primary B-ALL ... N Engl J Md 2009;360(5):470-480]. To discover the underlying pathways modulated by Ikaros we performed gene expression and gene ...
In three patients, resistance was associated with progressiveBCR-ABL gene amplification. These studies provide evidence that ... Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification ... Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification ... Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification ...
Exon 7 Deletion in the bcr-abl Gene Is Frequent in Chronic Myeloid Leukemia Patients and Is Not Correlated with Resistance ... Exon 7 Deletion in the bcr-abl Gene Is Frequent in Chronic Myeloid Leukemia Patients and Is Not Correlated with Resistance ... Exon 7 Deletion in the bcr-abl Gene Is Frequent in Chronic Myeloid Leukemia Patients and Is Not Correlated with Resistance ... Exon 7 Deletion in the bcr-abl Gene Is Frequent in Chronic Myeloid Leukemia Patients and Is Not Correlated with Resistance ...
With the T315I BCR-ABL Gene Mutation. Point mutations within the ABL kinase domain of the BCR-ABL gene are emerging as the most ... The patient will have the T315I BCR-ABL gene mutation. - Patients will have failed prior imatinib therapy. - ECOG performance ... With the T315I BCR-ABL Gene Mutation. Trial Phase:. Phase 2. Minimum Age:. 18 Years. Maximum Age:. N/A ...
ABL is a gene therapy CMO with expertise in developing processes and excuting GMP manufacturing to support cell & gene therapy ... ABL is an expert in developing and executing GMP manufacturing to support gene therapy products worldwide. With global virus ... ABL maintains single-use adherent and suspension platforms to produce gene therapy products: ... ABL can execute your gene therapy program efficiently and comprehensively. ...
ABL specializes in GMP viral vector manufacturing of AAV, VLPs, CMV, HSV-1, Vaccina and MVA, VSV, Adenovirus, retrovirus and ... From 30 years of groundbreaking work with HIV to supporting the latest gene therapy technologies, ABL offers a comprehensive ... ABL, Inc. Headquarters. 9800 Medical Center Drive, Building D. Rockville, MD 20850 USA. Toll Free: 800-225-5600. Phone: 301-881 ... ABL Lyon. Batiment Domilyon Centre dInfectiologie, Floor 1. 321 Avenue Jean Jaurès. 69007 Lyon FRANCE. Phone: +33 (0) 4 37 70 ...
... as a method to screen for mutations of the ABL gene.. METHODS: We used the dHPLC based assay for the screening of ABL point ... ABL gene kinase domain mutation scanning by denaturing high performance liquid chromatography sequencing method. Y cel Erbilgin ... ABL gene kinase domain mutation scanning by denaturing high performance liquid chromatography sequencing method. Turk J Hematol ... ABL geninin tirozin kinaz ve ATP b lgelerindeki nokta mutasyonlar d r. Bu al ma ABL gen mutasyonlar n n taranmas nda denat re ...
Expression of Pag also inhibits the in vitro kinase activity of c-Abl, but not SH3-mutated Abl or v-Abl. When transfected in ... We used the yeast two-hybrid system to identify a gene, PAG, whose protein product (Pag) interacts specifically with the Abl ... Inhibition requires the Abl SH3 and kinase domains and is not observed with other Abl SH3-binding proteins. ... Pag associates with c-Abl in vivo and inhibits tyrosine phosphorylation induced by overexpression of c-Abl. ...
1R2G1F signal pattern and the BCR/ABL fusion gene on der(9); B. 1R1G1F signal pattern and the BCR/ABL fusion gene on der(9) C. ... 2R1G1F signal pattern and the BCR/ABL fusion gene on der(22); D. 1R1G2F signal pattern and the BCR/ABL fusion genes on der(9) ... All experiments were performed in duplicate and the results were expressed as percent ratio to ABL. The BCR/ABL to ABL ratios ... In Ph-neg CML cases, the BCR/ABL fusion gene is often located on der(22) and rarely on der(9), indeed its presence on der(9) ...
Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571) ... Gene Product Annotation Gene Ontology Consortium Homepage. Chains. Polymer. Molecular Function. Biological Process. Cellular ... Abelsone tyrosine kinase (abl) Mouse (Mus musculus) [TaxId: 10090] B. d1iepb_. Alpha and beta proteins (a+b) Protein kinase- ... PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ABL (1IEP:A,B) * Protein Kinase Activity ...
C-abl gene. Many of the Philadelphia-positive adult ALL cases (50-75%) have a different type of gene rearrangement. The gene ... During the translocation, a part of the c-abl gene is fused to the first exon of the her gene (Fig. 14.5). The pl80BCR ABL ... Genes Dev. 11, 2456-2467. [Pg.207]. See other pages where C-abl gene is mentioned: [Pg.432] [Pg.432] [Pg.576] [Pg.13] [Pg.275] ... causing the ber and abl genes to fuse. The protein kinase encoded hy the bcr-abl gene is expressed at higher levels in cells ...
Plasmid pMal-Abl-PRM 5R from Dr. Michael Rosens lab contains the insert PRM-5R and is published in Nature. 2012 Mar 7;483(7389 ... Entrez Gene. ABL1 (a.k.a. ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, c-ABL1, p150, v-abl) ... Bacterial expression plasmid containing His and MBP tags for 5 PRM motif repeats of Human Abl. ... 5 repeats of the protein rich motif from proto-oncogene tyrosine-protein kinase (ABL) ...
BCR-ABL Gene Mutation Analysis Sometimes mutations occur in the part of the BCR-ABL1 gene that makes the BCR-ABL1 protein. ... A BCR-ABL1 gene mutation analysis is a test that looks for mutations in the BCR-ABL1 gene that may cause certain TKIs to stop ... This means that 0.1 percent of cells (1 out of every 1,000 cells) have the BCR-ABL1 gene. This is written as "BCR-ABL1 0.1%." ... This means that 10 percent of cells (10 out of every 100 cells) have the BCR-ABL1 gene. This is also written as "BCR-ABL1 10 ...
ABI1 gene. abl interactor 1. Enable Javascript to view the expand/collapse boxes.. Open All Close All ... From NCBI Gene:. This gene encodes a member of the Abelson-interactor family of adaptor proteins. These proteins facilitate ... chromosomal translocation involving this gene and the MLL gene has been associated with acute myeloid leukemia. Alternatively ... This gene may play a role in the progression of several malignancies including melanoma, colon cancer and breast cancer, and a ...
  • Overexpression of Abl-related gene tyrosine kinase ABL2 in pro-B cell line Ba/F3 cells expressing an oncogenic mutant of FLT3 (FLT3-ITD) resulted in partial inhibition of FLT3-ITD-dependent cell proliferation. (nih.gov)
  • Furthermore, LPS-induced airway lung inflammation was reduced by inhibition of c-Abl activity. (jimmunol.org)
  • The present study elucidated a novel signaling pathway to activate PARP1 and regulate gene expression, suggesting that blocking the interaction of c-Abl with PARP1 or pharmaceutical inhibition of c-Abl may improve the outcomes of PARP1 activation-mediated inflammatory diseases. (jimmunol.org)
  • Inhibition requires the Abl SH3 and kinase domains and is not observed with other Abl SH3-binding proteins. (escholarship.org)
  • Kinetic studies demonstrate that this compound is not ATP-competitive but is substrate-competitive and works synergistically with imatinib in wild-type BCR-ABL inhibition. (pnas.org)
  • Inhibition of c-Abl promotes the degradation of MST1 through C terminus of Hsc70-interacting protein (CHIP)-mediated ubiquitination, and thereby attenuates cell death. (jneurosci.org)
  • Inhibition of c-Abl by using c-Abl RNAi or STI571 attenuates oxidative stress-induced MST1 activation as well as cell death both in primary cultured neurons and in rat hippocampal neurons. (jneurosci.org)
  • Pharmacological inhibition using the selective c-Abl kinase inhibitor Gleevec confirmed that c-Abl plays an important role in Hp pathogenesis in a murine in vivo model. (springer.com)
  • Importantly, concurrent inhibition of NIK or c-Abl disrupts Aurora inhibitor-induced feedback activation of STAT3 and sensitizes myeloma cells to Aurora inhibitors, implicating a combined inhibition of Aurora and NIK or c-Abl kinases as potential therapies for multiple myeloma. (haematologica.org)
  • Accordingly, pharmacological inhibition of c-Abl together with Aurora resulted in substantial cell death and tumor regression in vivo . (haematologica.org)
  • The Abl family of tyrosine kinases is regulated by a complex set of intramolecular interactions that impinge both directly and indirectly on the Abl kinase domain and lead to effective inhibition of tyrosine kinase activity both in vitro and in vivo. (springer.com)
  • Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression. (jneurosci.org)
  • Compounds in this class (exemplified by GNF-2) show exclusive antiproliferative activity toward Bcr-abl-transformed cells, with potencies similar to imatinib, while showing no inhibition of the kinase activity of full-length or catalytic domain of c-abl. (nature.com)
  • Figure 3: Construct-dependent inhibition of abl activity by GNF-2. (nature.com)
  • Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. (nature.com)
  • They bind to DNA and control transcription of genes (activation or inhibition). (brainscape.com)
  • The enhanced responses of c-abl-/- osteoblasts could be mimicked by overexpression of PKC δ in normal cells and impeded by inhibition of PKC δ, and diminished responses of Atm-/- cells could be rescued by PKC δ overexpression, indicating that PKC δ mediated the effects of c-Abl and ATM in oxidative stress response. (columbia.edu)
  • Inhibition of Bcr-Abl kinase by STI571 results in FoxO3a activation, induction of Bim expression and apoptosis. (biomedsearch.com)
  • Human chronic myelogenous leukaemia is characterized by a reciprocal translocation between chromosomes 9 and 22 resulting in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of chromosome 22. (nih.gov)
  • In human leukemia, activation of the ABL proto-oncogene locus on chromosome 9 most commonly occurs as a result of its fusion to the BCR locus on chromosome 22. (aacrjournals.org)
  • BCR-ABL, a constitutively activated tyrosine kinase, is the oncogene that causes Philadelphia-chromosome-positive (Ph+) leukaemia. (nih.gov)
  • Translational regulation of the novel haploid-specific transcripts for the c-abl proto-oncogene and a member of the 70 kDa heat-shock protein gene family in the male germ line . (chempedia.info)
  • The Bcr/Abl oncogene results from a translocation (9;22) that fuses sequences from the BCR gene with the ABL gene. (aacrjournals.org)
  • Chronic myelogenous leukemia (CML) is a clonal malignancy of the hematopoietic stem cell harboring a 9;22 translocation which fuses the ABL proto-oncogene to the ABL gene leading to constitutive tyrosine kinase activity necessary and sufficient for massive overproduction of granulocytic cells ( 1 ). (aacrjournals.org)
  • This translocation fuses the breakpoint cluster region ( Bcr ) and the Abl genes and creates the BCR-ABL oncogene ( 4 ). (pnas.org)
  • The molecular consequence of the Ph chromosome is the generation of the BCR-ABL oncogene that encodes for the chimeric BCR-ABL oncoprotein, with constitutive kinase activity that promotes the growth advantage of leukemic cells ( 2 ). (aacrjournals.org)
  • Genes that are involved in cancer are divided into two categories: oncogene and tumor suppressor. (hindawi.com)
  • The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. (genome.jp)
  • This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. (abcam.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)
  • A fusion gene produced when a segment of the Abelson protooncogene, ABL, from chromosome 9, translocates to the major breakpoint cluster region (M-BCR) on chromosome 22. (thefreedictionary.com)
  • By analogy to the gag/abl fusion protein of Abelson murine leukemia virus, the replacement of amino terminal c-abl sequences by bcr sequences in P210 may create a transforming protein involved in CML. (sciencemag.org)
  • This gene encodes a member of the Abelson-interactor family of adaptor proteins. (nih.gov)
  • identified a member of the Abelson (Abl) family of tyrosine kinases, dAbl, as a regulator of Dsh in PCP signaling in the fruit fly. (sciencemag.org)
  • Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene. (wikipedia.org)
  • The Abelson murine leukaemia ( ABL) gene at 9q34 was targeted in this study as 9q34 is a common region of loss in NPC. (biomedcentral.com)
  • ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. (ox.ac.uk)
  • The symbol ABL is derived from Abelson , the name of a leukemia virus which carries a similar protein. (wikipedia.org)
  • These translocations fuse a breakpoint cluster region (BCR) derived from chromosome 22 to a portion of the c- ABL protooncogene from chromosome 9, thereby leading to formation of alternative BCR-ABL fusion proteins p210 BCR-ABL and p185 BCR-ABL (hereafter p210 and p185), which are typically detected in CML and Ph + ALL cells, respectively ( 3 - 5 ). (pnas.org)
  • Fusion genes are produced on chromosome 22, coding for various fusion proteins. (chempedia.info)
  • The most important fusion proteins are the p -and p -BCR-Abl hybrid proteins, which have increased Tyr kinase activity and an altered subcel-lular location. (chempedia.info)
  • Glutathione S -transferase (GST) pull-down assays with purified proteins identified the proline-rich region downstream of the PDZ domain of Dsh as the site of interaction with dAbl, and purified Abl phosphorylated both Dsh and the mouse homolog Dvl1 in the DEP (disheveled, Egl-10, pleckstrin) domain, which is required for membrane localization of Dsh and may mediate activation of downstream effectors. (sciencemag.org)
  • pAbl T735 interacted with 14-3-3 proteins, which caused cytoplasmic retention of c-Abl, where it potentiated Hp -mediated cell elongation and migration. (springer.com)
  • The exact mechanisms by which these rare fusion genes lead to blood cancer are not completely understood, although it is likely that the proteins produced from them promote uncontrolled growth of cells. (medlineplus.gov)
  • This increases the number of the phosphotyrosine residues on BCR-ABL and, as a consequence, the binding sites for the SH2 domains of other proteins ( 6, 7 ). (aacrjournals.org)
  • The latter results from the interaction of BCR-ABL with other cytoplasmic proteins, which function as adaptor molecules, thus creating multiprotein signaling complexes. (aacrjournals.org)
  • The fusion-proteins Bcr-Abl, Tel-Abl and v-Abl are three well-characterized examples in this respect. (springer.com)
  • In this chapter, we provide an overview of the mechanisms by which multiple cellular proteins transiently activate Abl kinases to perform cellular functions. (springer.com)
  • You will find three cellular RAS genes, encoding the K-ras, H-ras and N-ras proteins, and all display activating mutations in human being tumors. (movd2016.org)
  • Some types of cancer have a mutated HER2 gene that makes extra HER2 proteins and causes the cancer to grow. (cancer.ca)
  • The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. (genecards.org)
  • The symbol BCR is derived from breakpoint cluster region, a gene which encodes a protein that acts as a guanine nucleotide exchange factor for Rho GTPase proteins. (wikipedia.org)
  • Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a. (biomedsearch.com)
  • 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)
  • Chronic myelogenous leukemia (CML) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c-abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region (bcr) on chromosome 22. (sciencemag.org)
  • In this study, we show that, in response to LPS or TNF-α exposure, the nonreceptor tyrosine kinase c-Abl undergoes nuclear translocation and interacts with and phosphorylates PARP1 at the conserved Y829 site. (jimmunol.org)
  • The translocation moves the c-ABL gene that encodes a tyrosine kinase from chromosome 9 to the breakpoint cluster region fBCRj of chromosome 22. (chempedia.info)
  • Formation of a hybrid oncoprotein, illustrated by translocation of the Abl tyrosine kinase. (chempedia.info)
  • The gene for the Ser-spedfic protein kinase BCR is fused with a part of the c-abl gene in the process of the Philadelphia chromosome translocation. (chempedia.info)
  • Formation of the Bcr-Abl Gene by Translocation. (chempedia.info)
  • The protein kinase encoded hy the bcr-abl gene is expressed at higher levels in cells having this translocation than is the c-abl gene in normal cells. (chempedia.info)
  • During the translocation, a part of the c-abl gene is fused to the first exon of the her gene (Fig. 14.5). (chempedia.info)
  • It results from translocation between chromosomes 9 and 22 of the c-abl protooncogene, leading to the hybrid bcr-abl fusion gene on chromosome 22. (chempedia.info)
  • This gene may play a role in the progression of several malignancies including melanoma, colon cancer and breast cancer, and a t(10;11) chromosomal translocation involving this gene and the MLL gene has been associated with acute myeloid leukemia. (nih.gov)
  • Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. (aacrjournals.org)
  • However, the effects of BCR/ABL translocation on the capacity of dendritic cells to activate NK cells have never been studied. (aacrjournals.org)
  • Here we show that the BCR/ABL translocation specifically confers to dendritic cells a selective NK cell stimulatory function by up-regulating the expression of NKG2D ligands in both mouse and human models. (aacrjournals.org)
  • A genetic rearrangement (translocation) involving the ABL1 gene causes a type of cancer of blood-forming cells called chronic myeloid leukemia. (medlineplus.gov)
  • The translocation involved in this condition, written as t(9;22), fuses part of the ABL1 gene from chromosome 9 with part of the BCR gene from chromosome 22, creating an abnormal fusion gene called BCR-ABL1 . (medlineplus.gov)
  • This resulting translocation replaces the first exon of c- abl with sequences from the Bcr gene. (jci.org)
  • Chromosome studies, supplemented by fluorescence in situ hybridization (FISH) using the LSI BCR/ABL ES dual color translocation probe (Vysis Downer's Grove, IL, USA) and by M-FISH experiments, were performed on tumoral cells when the patient was referred to our department for the treatment of T-cell lymphoma in August 1999. (haematologica.org)
  • Translocation creates a bcr-abl fusion product. (brainscape.com)
  • This chromosome is defective and unusually short because of reciprocal translocation , t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22 , and contains a fusion gene called BCR-ABL1 . (wikipedia.org)
  • Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. (wikipedia.org)
  • The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). (abcam.com)
  • Mutation in the BCR-ABL kinase domain might be a frequent mechanism of STI571 resistance in lymphoid disease. (nih.gov)
  • Although several studies have attempted to address the mechanism(s) by which CML cells acquire imatinib resistance ( 8 - 10 ), most studies indicate that mutation of the BCR-ABL gene itself accounts for the majority of imatinib-resistant leukemias in vivo . (pnas.org)
  • Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T. Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. (medlineplus.gov)
  • Gündüz M, Özaydın E, Atar MB, Koç N, Kırsaçlıoğlu C, Köse G, Cefalù AB, Averna M, Tarugi P. Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up. (medlineplus.gov)
  • ABL gene kinase domain mutation scanning. (istanbul.edu.tr)
  • It is now evident that the phosphorylation of BCR Tyr177 is essential for BCR-ABL-mediated leukemogenesis ( 9 ), and its mutation largely abolishes GRB2 binding and diminishes BCR-ABL-induced Ras activation ( 7 ). (aacrjournals.org)
  • The aim of this study was to investigate clinical resistance to imatinib in Korean CML patients , and search for the point mutation of the BCR- ABL gene . (bvsalud.org)
  • Results K-RAS mutation detection assay We designed primers adjacent to codons 12, 13, 61 and 146 of the K-RAS gene, as these are the most common mutations in malignancy. (movd2016.org)
  • Most changes in a gene are because of a gene mutation. (cancer.ca)
  • It takes more than one gene mutation for a cell to become cancerous. (cancer.ca)
  • RNA-sequencing (seq) analysis on peripheral bold mononuclear cells of DDX41 mutation carriers with hematological malignancy (HM) revealed altered expression levels of genes involved in hemoglobin complex and innate immunity ( 17 ). (spandidos-publications.com)
  • These chromosomes have a specific gene mutation known as BCR-ABL , which helps the leukemia cells grow. (cancer.org)
  • Targeted drugs such as imatinib (Gleevec) and dasatinib (Sprycel) specifically attack cells that have this gene mutation. (cancer.org)
  • c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease. (nih.gov)
  • Tyrosine phosphorylation of PARP1 is crucial for NF-κB activation and gene expression. (jimmunol.org)
  • In a co-expression assay, Pag associates with c-Abl in vivo and inhibits tyrosine phosphorylation induced by overexpression of c-Abl. (escholarship.org)
  • Regulates ABL1/c-Abl-mediated phosphorylation of ENAH. (nih.gov)
  • Oxidative stress induces the c-Abl-dependent tyrosine phosphorylation of MST1 and increases the interaction between MST1 and FOXO3 (Forkhead box O3), thereby activating the MST1-FOXO signaling pathway, leading to cell death in both primary culture neurons and rat hippocampal neurons. (jneurosci.org)
  • c-Abl phosphorylation and localization were analyzed by immunostaining and immunofluorescence. (springer.com)
  • We report a novel mechanism and identified strong c-Abl threonine 735 phosphorylation (pAbl T735 ) mediated by the type-IV secretion system (T4SS) effector D-glycero-β-D-manno-heptose-1,7-bisphosphate (βHBP) and protein kinase C (PKC) as a new c-Abl kinase. (springer.com)
  • Importantly, in human patients suffering from Hp -mediated gastritis c-Abl expression and pAbl T735 phosphorylation were drastically enhanced as compared to type C gastritis patients or healthy individuals. (springer.com)
  • Accumulated NIK converts c-Abl tyrosine kinase from a nuclear proapoptotic into a cytoplasmic antiapoptotic effector by inducing its phosphorylation at Thr735, Tyr245 and Tyr412 residues, and, by entering into a trimeric complex formation with c-Abl and STAT3, increases both the transcriptional activity of STAT3 and expression of the antiapoptotic STAT3 target genes PIM1 and PIM2. (haematologica.org)
  • It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. (wikipedia.org)
  • The phosphorylation of c-Abl promotes actin polymerization. (wikipedia.org)
  • Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. (jneurosci.org)
  • Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2 (aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo . (jneurosci.org)
  • Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. (jneurosci.org)
  • 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)
  • The resulting chimeric BCR/ABL fusion gene encodes for constitutively active tyrosine kinase protein [ 3 ]. (oncotarget.com)
  • The recombinant gene encodes a tyrosine kinase mutant with unregulated (constitutive), enhanced activity that promotes cell proliferation . (chempedia.info)
  • CFTR gene, which encodes a transmembrane ion channel, cause mucus buildup in the airways of patients with cystic fibrosis. (hhmi.org)
  • 2 min 31 sec) Mutations in the CFTR gene, which encodes a transmembrane ion channel, cause mucus buildup in the airways of patients with cystic fibrosis. (hhmi.org)
  • This gene encodes an ETS family transcription factor. (genecards.org)
  • This gene encodes for a BCR-ABL fusion protein. (wikipedia.org)
  • The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. (genome.jp)
  • Mouse bone marrow cells transduced with retroviral vectors encoding either of two oncogenic Bcr-Abl isoforms (p210 Bcr-Abl and p185 Bcr-Abl ) induce B cell lympholeukemias when transplanted into lethally irradiated mice. (pnas.org)
  • The oncogenic Bcr-Abl tyrosine kinase activates various signaling pathways including phosphoinositide 3-kinase/Akt and nuclear factor-κB that mediate proliferation, transformation, and apoptosis resistance in Bcr-Abl(+) myeloid leukemia cells. (aacrjournals.org)
  • Most excitingly, the majority of the principles appearing to govern c-Abl and Arg are still operational in the Bcr-Abl oncogenic counterpart and affect the efficacy of small molecular ATP-competitors. (springer.com)
  • Oncogenic gene translocations occur in acute leukemia. (ox.ac.uk)
  • However, unlike the e8a2 transcripts previously described,8-10 the direct junction between BCR exon e8 and ABL exon a4 led to the preservation of the ORF encompassing the whole oncogenic domains of the ABL tyrosine kinase. (haematologica.org)
  • The number of e8a4 copies in the non diluted sample was estimated to be 13,600 for 10,000 copies of ABL which agreed with data obtained by cytogenetic analysis and confirmed that the e8a4 must be the oncogenic fusion transcript. (haematologica.org)
  • 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)
  • 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)
  • Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). (wikipedia.org)
  • The qPCR test measures the number of cells that have the BCR-ABL1 gene. (lls.org)
  • This means that 10 percent of cells (10 out of every 100 cells) have the BCR-ABL1 gene. (lls.org)
  • The ABL1 gene provides instructions for making a protein involved in many processes in cells throughout the body. (medlineplus.gov)
  • ABL1 can also help regulate the activity of other genes. (medlineplus.gov)
  • The ABL1 gene belongs to a class of genes known as oncogenes. (medlineplus.gov)
  • The abnormal chromosome 22, containing a piece of chromosome 9 and the BCR-ABL1 fusion gene, is commonly called the Philadelphia chromosome. (medlineplus.gov)
  • The protein produced from the abnormal fusion gene, called BCR-ABL1, functions as a kinase. (medlineplus.gov)
  • The BCR-ABL1 fusion gene (described above) is also involved in fast-growing blood cell cancers called acute leukemias. (medlineplus.gov)
  • Rarely, translocations that lead to fusion of the ABL1 gene with genes other than BCR are associated with acute leukemias. (medlineplus.gov)
  • For example, the ETV6-ABL1 fusion gene has been found in a small number of cases of B-cell acute lymphoid leukemia, and a chronic leukemia that can resemble chronic myeloid leukemia. (medlineplus.gov)
  • Evidence that has accumulated over the last years points to c-Abl and Arg (ABL1 and ABL2) as being particular forms of the Src family of kinases. (springer.com)
  • This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signalling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle. (wikipedia.org)
  • The result is that a fusion gene is created by juxtaposing the ABL1 gene on chromosome 9 (region q34) to a part of the BCR (breakpoint cluster region) gene on chromosome 22 (region q11). (wikipedia.org)
  • The Abl gene expresses a membrane-associated protein, a tyrosine kinase , and the BCR-Abl transcript is also translated into a tyrosine kinase containing domains from both the BCR and ABL1 genes. (wikipedia.org)
  • As the N-terminal Y177 and CC domains from BCR encode the constitutive activation of the ABL1 kinase, these regions are targeted in therapies to downregulate BCR-ABL kinase activity. (wikipedia.org)
  • The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of actin dynamics and localizes to the tips of lamellipodia and filopodia. (asm.org)
  • This complex includes Nap-1, Pir121, HSPC300, and Abl interactor 2 (Abi-2) ( 12 ). (asm.org)
  • Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. (wikipedia.org)
  • Nuclear c-Abl has been shown to have an important role in damage-induced apoptosis. (chempedia.info)
  • Other compounds, such as PD180970 and CGP76030, both of which inhibit BCR-ABL by binding to the ATP-binding site, have been shown to induce apoptosis in a few select cases of imatinib-resistant CMLs ( 13 - 16 ). (pnas.org)
  • In mammalian neurons, oxidative stress activates c-Abl, which phosphorylates and activates the MST1-FOXO3 signaling cascade and promotes neuron apoptosis. (jneurosci.org)
  • Interestingly, c-Abl contains nuclear import and export signals, and the nuclear c-Abl inhibits differentiation and promotes apoptosis in response to genotoxic stress. (biologists.org)
  • This study aimed to identify the chromosome breakages and/or rearrangements in the ABL gene in cells undergoing oxidative stress-induced apoptosis. (biomedcentral.com)
  • By using inverse polymerase chain reaction (IPCR), we demonstrated that hydrogen peroxide (H 2 O 2 )-induced apoptosis in normal nasopharyngeal epithelial and NPC cells led to chromosomal breakages within the ABL BCR that contains a MAR/SAR. (biomedcentral.com)
  • Figure 2: GNF-2 blocks proliferation and induces apoptosis of Ba/F3 cells expressing wild-type Bcr-abl and the E255V mutant. (nature.com)
  • Tumour suppressor genes are normal genes that slow cell growth and division, repair mistakes in DNA and tell cells when to die (a normal process called apoptosis or programmed cell death). (cancer.ca)
  • Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells. (biomedsearch.com)
  • In this study, we have used the human BV173 and the mouse BaF3/Bcr-Abl-expressing cell lines as model systems to investigate the molecular mechanisms whereby STI571 and FoxO3a regulate Bim expression and apoptosis. (biomedsearch.com)
  • Conversely, silencing of FoxO3a in Bcr-Abl-expressing cells abolishes STI571-mediated Bim induction and apoptosis. (biomedsearch.com)
  • In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. (wikipedia.org)
  • In CML patients, between 73% and 100% of monocyte-derived dendritic cells (CML dendritic cells) are positive for the chimeric ABL/ABL gene ( 19 , 20 ). (aacrjournals.org)
  • Mice receiving Arf −/− or Arf +/− p210 Bcr-Abl -positive pre-B cells do not achieve remission when maintained on high doses of oral imatinib therapy and rapidly succumb to lympholeukemia. (pnas.org)
  • Treatment of Arf −/− , p210 Bcr-Abl -positive pre-B cells with imatinib together with an inhibitor of JAK kinases abrogates this resistance, suggesting that this combination may prove beneficial in the treatment of BCR-ABL-positive acute lymphoblastic leukemia. (pnas.org)
  • The fusion gene produces a specific protein, P210. (thefreedictionary.com)
  • CML cells have two novel products: an 8.5-kilobase RNA transcript containing both abl and bcr and a 210-kilodalton phosphoprotein (P210) recognized by v-abl-specific antisera. (sciencemag.org)
  • To test whether the P210 is the product of the novel 8.5-kilobase bcr/abl fusion transcript, antibodies were prepared against c-abl and bcr determinants. (sciencemag.org)
  • By using these reagents and v-abl-specific antisera, it was demonstrated that the P210 in CML cells is indeed the protein product of the 8.5-kilobase transcript. (sciencemag.org)
  • Elevated expression of a subset of interferon inducible genes in primary bone marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray analysis. (duke.edu)
  • p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than p210 Bcr-Abl. (duke.edu)
  • A group of interferon-gamma-inducible genes, including those encoding a family of 47 kDa GTPases, were significantly increased in p185 versus p210. (duke.edu)
  • Consequently, the hybrid BCR-ABL fusion protein is referred to as p210 or p185. (wikipedia.org)
  • Three clinically important variants encoded by the fusion gene are the p190, p210, and p230 isoforms. (wikipedia.org)
  • There is some evidence that the expression of Abl is regulated by the microRNA miR-203. (wikipedia.org)
  • Our results support the participation of the c-Abl/HDAC2 signaling pathway in the epigenetic blockade of gene expression in AD pathology. (nih.gov)
  • however, the precise mechanisms by which PARP1 is activated independent of DNA damage, and thereby playing a role in expression of inflammatory genes, remain poorly understood. (jimmunol.org)
  • Tyrosine-phosphorylated PARP1 is required for protein poly(ADP-ribosyl)ation of RelA/p65 and NF-κB-dependent expression of proinflammatory genes in murine RAW 264.7 macrophages, human monocytic THP1 cells, or mouse lungs. (jimmunol.org)
  • Ikaros deletions in BCR-ABL-negative childhood acute lymphoblastic leukemia are associated with a distinct gene expression signature but do not result in intrinsic chemoresistance. (sigmaaldrich.com)
  • To discover the underlying pathways modulated by Ikaros we performed gene expression and gene ontology analysis in IKZF1 deleted primary B-ALL pediatric patient samples. (sigmaaldrich.com)
  • We report a specific gene expression signature of 735 up-regulated and 473 down-regulated genes in IKZF1 deleted primary B-ALL pediatric patient samples. (sigmaaldrich.com)
  • Expression of Pag also inhibits the in vitro kinase activity of c-Abl, but not SH3-mutated Abl or v-Abl. (escholarship.org)
  • Bacterial expression plasmid containing His and MBP tags for 5 PRM motif repeats of Human Abl. (addgene.org)
  • We show that xanthohumol strongly inhibited Bcr-Abl expression at both mRNA and protein levels and show that xanthohumol caused elevation of intracellular reactive oxygen species and that the antioxidant N -acetylcysteine blunted xanthohumol-induced events. (aacrjournals.org)
  • As structural mutations and/or gene amplification in Bcr-Abl can circumvent an otherwise potent anticancer drug such as imatinib, targeting Bcr-Abl expression as well as its kinase activity could be a novel additional therapeutic approach for the treatment of Bcr-Abl(+) myeloid leukemia. (aacrjournals.org)
  • Bcr/Abl has also been implicated as a possible regulator of CML angiogenesis associated with elevated vascular endothelial growth factor (VEGF) expression levels ( 5 ). (aacrjournals.org)
  • BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. (aacrjournals.org)
  • 10 ) have recently shown that ABL/ABL directly alters the function of NK cells (i.e., induces partial IL-2 independent growth and increases killer immunoglobulin-like receptor expression in primary CD56 bright NK cell subsets). (aacrjournals.org)
  • Epigenetic research, i.e. the evaluation of heritable gene expression patterns without changes in the DNA sequence, has primarily focussed on the regulation of highly coordinated developmental changes of cells and organisms, as well as disturbances of epigenetic mechanisms in hereditary and acquired human diseases, including cancer. (dfg.de)
  • By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1? (ablkinase.com)
  • We have recently demonstrated that loss of expression of the ABI3BP (ABI3-binding protein) gene is common to all thyroid carcinomas, and that ABI3BP re-expression altered tumor growth by increasing senescence and inhibiting invasion and migration. (unifesp.br)
  • Utilizando a técnica de SAGE (do inglês, Serial Analysis of Gene Expression), verificamos que o transcrito do gene ABI3BP (ABI3-Binding Protein) encontra-se presente nas bibliotecas SAGE geradas a partir de tiróide normal e de adenoma folicular da tireóide e ausente na biblioteca derivada de carcinoma folicular da tiróide. (unifesp.br)
  • In this study, we examined differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct phenotypes produced by the two Bcr-Abl forms. (duke.edu)
  • Significant differences in gene expression were observed on hierarchical clustering. (duke.edu)
  • Follow the symbol links to get more information on the GO terms, expression assays, orthologs, phenotypic alleles, and other information for the genes or markers below. (jax.org)
  • In this hands-on activity students review the steps of eukaryotic gene expression and learn how this knowledge can be used to treat genetic disease. (hhmi.org)
  • Scientists studied how the dominance ranking of female rhesus macaques living in social groups affected the expression of genes linked to immune response. (hhmi.org)
  • In this activity students analyze data on the expression of the tb1 gene and use it to formulate an explanation as to how a specific difference in the corn version of the gene explains the phenotype of less branching. (hhmi.org)
  • Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized at the molecular level by the expression of Bcr-abl, a 210-kDa fusion protein with deregulated tyrosine kinase activity. (nature.com)
  • Fig. 1 Increased expression of ABL genes in invasive breast cancer is associated with metastasis. (sciencemag.org)
  • Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. (benthamscience.com)
  • Cancer genes, involved in autonomous, unregulated cell proliferation in cancer cells, expression is constitutive, only one mutant allele required (gain of function). (brainscape.com)
  • These phenotypes correlated with increased PKC δ expression in c-abl-/- osteoblasts and decreased PKC δ expression in Atm-/- cells, respectively. (columbia.edu)
  • DDX41 selectively upregulated the expression levels of five antigen processing and presentation genes (HSPA1A, HSPA1B, HSPA6, HLA‑DMB and HLA‑G) and downregulated other immune‑response genes in HeLa cells. (spandidos-publications.com)
  • GXD's primary emphasis is on endogenous gene expression during development. (jax.org)
  • This drug resistance is most often due to selection for secondary mutations in the BCR-ABL oncoprotein, rather than to "downstream" mutations affecting the signaling pathways subverted by the BCR-ABL kinase ( 8 ). (pnas.org)
  • The class-I carcinogen Helicobacter pylori ( Hp ) activates the non-receptor tyrosine kinase c-Abl to phosphorylate the oncoprotein cytotoxin-associated gene A (CagA). (springer.com)
  • Abnormal interactions between the BCR-ABL oncoprotein and other cytoplasmic molecules lead to the disruption of key cellular processes. (aacrjournals.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)
  • Although the ABL kinase inhibitor imatinib mesylate (Gleevec) provides highly effective treatment for BCR-ABL-positive chronic myelogenous leukemia, it has proven far less efficacious in the treatment of BCR-ABL-positive acute lymphoblastic leukemias (ALLs), many of which sustain deletions of the INK4A-ARF ( CDKN2A ) tumor suppressor locus. (pnas.org)
  • This fusion gene is found in chronic myelocytic leukemia (CML). (thefreedictionary.com)
  • Ikaros, the product of IKZF1, is a regulator of lymphoid development and polymorphisms in the gene have been associated with the acute lymphoblastic leukemia (ALL). (sigmaaldrich.com)
  • Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. (sciencemag.org)
  • At diagnosis, about 5% of Chronic Myeloid Leukemia (CML) patients lacks Philadelphia chromosome (Ph), despite the presence of the BCR/ABL rearrangement. (oncotarget.com)
  • In chronic myologenous leukemia, parts of chromosomes 9 and 22 are reciprocally exchanged, causing the ber and abl genes to fuse. (chempedia.info)
  • Several types of mutations of the ABL gene ean be found in chronic myeloid leukemia patients resistant to STI571, and they ean pre-exist to the onset of treatment. (chempedia.info)
  • The discovery that Bcr/Abl is required for the pathogenesis of chronic myelogenous leukemia (CML) and that the tyrosine kinase activity of ABL is essential for Bcr/Abl-mediated transformation made the ABL kinase an attractive target for clinical intervention ( 1 ). (aacrjournals.org)
  • Based on our reported antiendothelial effects of xanthohumol and on the observation that endothelial and hematopoietic cells are mutually correlated in their development and growth, here we investigated the effects of xanthohumol on Bcr/Abl-expressing leukemia cells. (aacrjournals.org)
  • Imatinib (also called Gleevec or STI571) is a small-molecule inhibitor that binds to the kinase domain of BCR-ABL and stabilizes the protein in its closed, inactive conformation ( 5 ), thereby inhibiting its activity, and is now a first-line therapy for the majority of chronic myelogenous leukemia (CML) cases because of its high efficacy level and relatively mild side effects ( 6 ). (pnas.org)
  • Detection of BCR-ABL gene mutations in chronic myeloid leukemia using biochips]. (cdc.gov)
  • Deregulated c-Abl activity has been intensively studied in a variety of solid tumors and leukemia. (springer.com)
  • Identification of Philadelphia chromosome or BCR/ABL gene rearrangement in chronic myeloid leukemia is important at diagnosis as well as after treatment. (scielo.br)
  • Aberrant tyrosine kinase activity plays a critical role in many hematologic disorders, including chronic myeloid leukemia characterized by the constitutive activity of BCR-ABL. (aacrjournals.org)
  • The deregulated tyrosine kinase activity of BCR-ABL has been shown to be necessary and sufficient to maintain the leukemia phenotype of CML ( 3-5 ). (aacrjournals.org)
  • Imatinib mesylate , the tyrosine kinase activity of the BCR-ABL fusion gene , induces a remarkable remission in chronic myeloid leukemia (CML) patients . (bvsalud.org)
  • We report a chronic myeloid leukemia patient without evidence of a Philadelphia (Ph) chromosome in whom RT-PCR analysis performed in blast crisis demonstrated the existence of both common b3a2 and b2a2 BCR/ABL fusion transcripts. (unl.pt)
  • This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. (genecards.org)
  • This study describes the use of denaturing high performance liquid chromatography (dHPLC) as a method to screen for mutations of the ABL gene. (tjh.com.tr)
  • Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib. (wikipedia.org)
  • Treatment of CML has been revolutionized by the advent of specific ABL tyrosine kinase inhibitors now used in the front-line management of this disease ( 7 ). (pnas.org)
  • Therefore, second-generation kinase inhibitors, such as dasatinib, that effectively block the activity of most mutant forms of BCR-ABL are now being used to treat imatinib-resistant CML ( 9 , 10 ). (pnas.org)
  • In our quest to develop new BCR-ABL inhibitors, we chose to target regions outside the ATP-binding site of this enzyme because these compounds offer the potential to be unaffected by mutations that make CML cells resistant to imatinib. (pnas.org)
  • Because of the frequency of mutations within the kinase domain, efforts are now focused on the identification of novel inhibitors that are active against imatinib-resistant mutants of BCR-ABL. (pnas.org)
  • In the last 15 years the introduction of techniques for identifying and measuring BCR-ABL transcripts has enabled more precise assessment of response to specific therapies for CML, notably the use of allogeneic stem cell transplantation, interferon-α, and tyrosine kinase (TK) inhibitors. (bloodjournal.org)
  • A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. (cdc.gov)
  • Here, we discover a NF-κB-inducing kinase (NIK)-c-Abl-STAT3 signaling-centered feedback loop that restrains the efficacy of Aurora inhibitors in multiple myeloma. (haematologica.org)
  • The functional disruption of any of the components of the trimer NIK-c-Abl-STAT3 or the PIM survival kinases consistently enhances the responsiveness of myeloma cells to Aurora inhibitors. (haematologica.org)
  • The findings reveal an important functional interaction between NIK, Abl and Aurora kinases, and identify the NIK, c-Abl and PIM survival kinases as potential pharmacological targets for improving the efficacy of Aurora inhibitors in myeloma. (haematologica.org)
  • This structure may therefore serve as a tool for the development of allosteric ABL inhibitors. (ox.ac.uk)
  • We report the discovery of a new class of Bcr-abl inhibitors using an unbiased differential cytotoxicity screen of a combinatorial kinase-directed heterocycle library. (nature.com)
  • Common secondary abnormalities include mutations in TP53, RB, and p16/INK4A, or overexpression of genes such as EVI1. (genome.jp)
  • Targeting signaling pathways activated by Bcr/Abl is a promising approach for drug development. (aacrjournals.org)
  • Our results identify new signaling pathways upstream and downstream of Bcr/Abl that are targeted by xanthohumol and suggest it may be of therapeutic utility in patients with CML. (aacrjournals.org)
  • Here, we investigated the activity and subcellular localization of c-Abl in vitro and in vivo and unraveled the contribution of c-Abl in CagA-dependent and -independent pathways to gastric Hp pathogenesis. (springer.com)
  • Recent genetic evidence has established a pathogenetic role for NF-κB signaling in MM. 4 2 In particular, at various frequencies, MM cells harbor gain-of-function mutations as well as loss-of-function mutations in genes encoding components of the classical and the alternative NF-κB pathways. (haematologica.org)
  • 4 2 Among these, mutations in the genes encoding NF-κB-inducing kinase (NIK) or its negative regulators TRAF2, TRAF3, cIAP1, and cIAP2 lead to increased stability of NIK and subsequent aberrant activation of the non-canonical and canonical NF-κB pathways. (haematologica.org)
  • Among its related pathways are Hematopoietic Stem Cell Gene Regulation by GABP alpha/beta Complex and Transcriptional misregulation in cancer . (genecards.org)
  • The fused BCR-ABL protein interacts with the interleukin-3 receptor beta(c) subunit and is moderated by an activation loop within its SH1 domain, which is turned "on" when bound to ATP and triggers downstream pathways. (wikipedia.org)
  • DDX41 selectively regulated the alternative splicing of genes in cancer‑associated pathways including the EGFR and FGFR signaling pathways. (spandidos-publications.com)
  • Transcription factor that activates a wide range of genes. (brainscape.com)
  • Oncogenes are mutated genes that cause cells to grow out of control and can lead to cancer. (cancer.ca)
  • Proto-oncogenes are normal genes that control cell growth but if they become mutated they can turn into oncogenes. (cancer.ca)
  • When DNA repair genes are mutated, they can't fix mistakes in oncogenes and tumour suppressor genes, and this can lead to cancer. (cancer.ca)
  • Additionally, DDX41‑regulated oncogenes and antigen processing and presentation genes were associated with patient survival rates. (spandidos-publications.com)
  • Characterization of an 8-kilobase RNA specific to chronic myelogenous leukaemia shows it to be a fused transcript of the two genes. (nih.gov)
  • Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 14. (nih.gov)
  • 1 - 3 In 1993 Cross and colleagues introduced a competitive technique that allowed transcript numbers to be expressed per microgram of leukocyte RNA 4 or as a ratio of BCR-ABL/ABL on a log scale. (bloodjournal.org)
  • Several transcript variants encoding multiple isoforms have been found for this gene. (wikipedia.org)
  • Molecular analyses identified a new transcript, an e8a4 BCR-ABL fusion mRNA which could be responsible for the disease transformation. (haematologica.org)
  • Activation of the ABL tyrosine kinase is a primary event in the genesis of CML, as shown by the retrovirally mediated insertion of a human BCR-ABL gene into murine hematopoietic stem cells and the creation of BCR-ABL transgenic mice ( 3 ). (aacrjournals.org)
  • Imatinib, which is an inhibitor of the BCR-ABL tyrosine kinase, has been a remarkable success for the treatment of Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemias (CMLs). (pnas.org)
  • Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. (genome.jp)
  • Imatinib mesylate (Gleevec, STI-571) is a selective tyrosine kinase inhibitor that has been proven to be a powerful agent for leukemias caused by Bcr/Abl, but the emergence of imatinib resistance underscores the need for additional therapies ( 2 ). (aacrjournals.org)
  • 10 nM concentration in vitro and cause regression of leukemias induced by i.v. injection of 32Dcl3 cells expressing the imatinib-resistant BCR-ABL isoform T315I. (pnas.org)
  • The aminoterminal BCR -encoded sequences of BCR-ABL contain a tyrosine-phosphorylated site that binds the SH2 domain of the adaptor protein GRB2 ( 6 ). (aacrjournals.org)
  • Promoter analysis The gene annotations and repeat-masked genome sequences for six mammalian species including human being, marmoset, mouse, rat, cow, pig had been downloaded from ENSEMBL (edition 62). (ablkinase.com)
  • We used the yeast two-hybrid system to identify a gene, PAG, whose protein product (Pag) interacts specifically with the Abl SH3 domain. (escholarship.org)
  • It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. (wikipedia.org)
  • The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST1 suggests that the c-Abl-MST1 signaling cascade plays an important role in cellular responses to oxidative stress. (jneurosci.org)
  • Recently, c-Abl has been linked to oxidative stress-induced neuronal cell death through Cdk5/GSK3β activation and Tau hyperphosphorylation or through p73 upregulation. (jneurosci.org)
  • Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. (jneurosci.org)
  • Since oxidative stress is a prominent feature of sporadic PD ( Jenner and Olanow, 1998 ), we investigated whether c-Abl could play pathogenic role in PD. (jneurosci.org)
  • c-Abl and Atm have been implicated in cell responses to DNA damage and oxidative stress. (columbia.edu)
  • In this report, we show that deficiency of c-Abl and deficiency of ATM differentially altered cell responses to oxidative stress by induction of antioxidant protein peroxiredoxin I (Prx I) via Nrf2 and cell death, both of which required protein kinase C (PKC) δ activation and were mediated by reactive oxygen species. (columbia.edu)
  • Hence, our results unveiled a previously unrecognized mechanism by which c-Abl and Atm participate in oxidative stress response. (columbia.edu)
  • We found that c-Abl phosphorylates the Y433 of MST1 kinase at the C terminus, leading to the stabilization and activation of MST1 as well as enhanced interaction with FOXO3. (jneurosci.org)
  • Just as much as or even more than the Src kinases, Abl members are built to be able to couple protein-protein interaction with protein tyrosine kinase catalytic output. (springer.com)
  • Barilá D, Superti-Furga G. An intramolecular SH3-domain interaction regulates c-Abl activity. (springer.com)
  • The most important mechanisms known to cause resistance are point mutations in the ABL tyrosine kinase and the ATP domain. (tjh.com.tr)
  • ref. 4 ) has emerged as essential signaling mechanisms in Bcr/Abl leukemogenesis. (aacrjournals.org)
  • We present the entire set of mechanisms that lead to Abl activation, grouping the numerous studies on physiological stimuli acting on Abl into distinct activation categories. (springer.com)
  • The recently obtained insights into the structure of autoinhibited Abl is integrated and is used as guide to explain the different molecular mechanisms. (springer.com)
  • Pendergast AM. The Abl family kinases: Mechanisms of regulation and signaling. (springer.com)
  • We propose that this new class of compounds inhibits Bcr-abl kinase activity through an allosteric non-ATP competitive mechanism. (nature.com)
  • We have identified a novel activation of ABL which involves a gene located on chromosome 12, designated TEL . Like BCR, TEL is fused in-frame with ABL and produces a fusion protein with an elevated tyrosine kinase activity when assayed in an immune complex. (aacrjournals.org)
  • Abl family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus. (nih.gov)
  • Abl tyrosine kinases phosphorylate Dsh to influence planar cell polarity without affecting canonical Wnt signaling. (sciencemag.org)
  • Colicelli J. ABL tyrosine kinases: evolution of function, regulation, and specificity. (medlineplus.gov)
  • On the other hand, the controlled activation of Abl kinases is required for a large number of normal cellular processes. (springer.com)
  • Hantschel O, Superti-Furga G. Regulation of the c-Abl and Bcr-Abl Tyrosine Kinases. (springer.com)
  • Among the tyrosine kinases, c-Abl and its relative Arg are unique in binding directly to F-actin. (biologists.org)
  • c-Abl is structurally homologous to the Src family of kinases in its N-terminal region, with three distinct domains-SH3, SH2, and a tyrosine kinase catalytic domain ( Smith and Mayer, 2002 ). (jneurosci.org)
  • Fig. 2 Knockdown of ABL kinases decreases breast cancer bone metastasis. (sciencemag.org)
  • Fig. 4 ABL kinases are required for tumor survival and tumor-induced osteolysis in the bone microenvironment. (sciencemag.org)
  • The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases. (mdpi.com)
  • The activity of tyrosine kinases is typically regulated in an auto-inhibitory fashion, but the BCR-Abl fusion gene codes for a protein that is "always on" or constitutively activated, leading to impaired DNA binding and unregulated cell division (i.e. cancer). (wikipedia.org)
  • Tumor suppressor genes are protein-coding genes that suppress cell division, such as RB1 and p53. (hindawi.com)
  • What is the function of tumor suppressor genes? (brainscape.com)
  • How do mutations need to occur in tumor suppressor genes for oncogenesis? (brainscape.com)
  • ABL tyrosine kinase activity is constitutively activated by the juxtaposition of BCR, thus favoring dimerization or tetramerization and subsequent autophosphorylation. (aacrjournals.org)
  • The BCR-ABL/GRB2 complex recruits Son of Sevenless (SOS), which is constitutively associated with the GRB2 SH3 domain ( 10 ). (aacrjournals.org)
  • FoxO3a lies downstream of Bcr-Abl signalling and is constitutively phosphorylated in the Bcr-Abl-positive BV173 and BaF3/Bcr-Abl cells. (biomedsearch.com)
  • Gene ontology studies revealed an up-regulation of genes associated with cell adhesion, cytoskeletal regulation, and motility in IKZF deleted patient samples. (sigmaaldrich.com)
  • Importantly, the involvement of Abl sheds light on pathway-specific Dsh regulation. (sciencemag.org)
  • Mayer BJ, Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. (springer.com)
  • Gene involved in destruction and down-regulation of B-catenin. (brainscape.com)
  • A larger PCR analysis using a forward primer in the BCR gene (ENF4026) and a reverse primer (5'GCCCTCGTACAC-CTCCCCGTA3') in the ABL exon a4 revealed an atypical e8a4 after direct sequencing (Figure 1B). (haematologica.org)
  • The quantification of the e8a4 was carried out using RQ-PCR with an e8 forward primer from BCR gene,10 the same reverse primer and a new probe (FAM 5'TCTACGTCTC-CTCCGAGAGC3'TAMRA) in ABL exon a4. (haematologica.org)
  • Biochemical and genetic evidence suggests that the tyrosine kinase activity of c-Abl is tightly regulated in vivo by a cellular factor binding to the Src homology 3 (SH3) domain of Abl. (escholarship.org)
  • Van Etten RA (1999) Cycling, stressed-out and nervous cellular functions of c-Abl. (chempedia.info)
  • The modular structure and the nuclear-cytoplasmic shuttling of c-Abl suggest that it integrates multiple signals to coordinate F-actin dynamics with the cellular decision to differentiate or to die. (biologists.org)
  • Background The RAS genes encode a family of GTPases that act as signal switch molecules for many important cellular processes. (movd2016.org)
  • c-Abl is a tightly regulated non-receptor protein tyrosine kinase involved in a wide range of cellular processes, including growth, survival and stress response ( Hantschel and Superti-Furga, 2004 ). (jneurosci.org)
  • When transfected in NIH-3T3 cells, Pag is localized to nucleus and cytoplasm and rescues the cytostatic effect induced by c-Abl. (escholarship.org)
  • Here, we show that xanthohumol has in vitro activity against Bcr-Abl(+) cells and clinical samples and retained its cytotoxicity when imatinib mesylate-resistant K562 cells were examined. (aacrjournals.org)
  • Many of the Philadelphia-positive adult ALL cases (50-75%) have a different type of gene rearrangement . (chempedia.info)
  • and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing BCR-ABL kinase domain mutations. (bloodjournal.org)
  • Figure 4: GNF-2 binds recombinant abl and Bcr-abl. (nature.com)
  • At a molecular level, there is rearrangement of the BCR and ABL genes with the function of codifying a fusion protein with increased and deregulated tyrosine kinase activity. (scielo.br)
  • Trends Cell Biol 9 179-186 Van Etten RA et al (1989) The mouse type IV c-abl gene product is a nuclear protein , and activation of transforming ability is associated with cytoplasmic localization. (chempedia.info)
  • We aimed to find out whether point mutations in BCR-ABL cause resistance to STI571. (nih.gov)
  • Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. (sciencemag.org)
  • In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. (sciencemag.org)
  • In three patients, resistance was associated with progressive BCR-ABL gene amplification. (sciencemag.org)
  • Point mutations within the ABL kinase domain of the BCR-ABL gene are emerging as the most frequent mechanism for resistance to imatinib and resultant reactivation of kinase activity. (knowcancer.com)
  • OBJECTIVE: Despite the efficacy of the BCR-ABL tyrosine kinase inhibitor imatinib, the development of resistance against imatinib has been observed. (tjh.com.tr)
  • Therapy resistance was observed in one patient with duplication of BCR/ABL rearrangement and in another one with high risk. (oncotarget.com)
  • However, a significant proportion of patients chronically treated with imatinib develop resistance because of the acquisition of mutations in the kinase domain of BCR-ABL. (pnas.org)
  • However, resistance to imatinib has been observed in a significant proportion of subjects, with the point mutations of the BCR-ABL kinase domain clinically identified as a possible mechanism. (bvsalud.org)