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.
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.
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)
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.
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
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.
BENZOIC ACID amides.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
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%.
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.
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).
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
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.
Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.
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.
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
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).
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
Progenitor cells from which all blood cells derive.
An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.
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)
A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.
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.
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.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.
The short, acrocentric human chromosomes, called group G in the human chromosome classification. This group consists of chromosome pairs 21 and 22 and the Y chromosome.
Therapeutic act or process that initiates a response to a complete or partial remission level.
Mapping of the KARYOTYPE of a cell.
A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of "hairy" or "flagellated" cells in the blood and bone marrow.
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
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.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
The type species of DELTARETROVIRUS that causes a form of bovine lymphosarcoma (ENZOOTIC BOVINE LEUKOSIS) or persistent lymphocytosis.
A species of GAMMARETROVIRUS causing leukemia, lymphosarcoma, immune deficiency, or other degenerative diseases in cats. Several cellular oncogenes confer on FeLV the ability to induce sarcomas (see also SARCOMA VIRUSES, FELINE).
Agents that inhibit PROTEIN KINASES.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
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.
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.
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
Established cell cultures that have the potential to propagate indefinitely.
Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.
A specific pair of GROUP C CHROMSOMES of the human chromosome classification.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
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.
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.
Disease having a short and relatively severe course.
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.
A rare myeloproliferative disorder that is characterized by a sustained, mature neutrophilic leukocytosis. No monocytosis, EOSINOPHILIA, or basophilia is present, nor is there a PHILADELPHIA CHROMOSOME or bcr-abl fusion gene (GENES, ABL).
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
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.
A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
RNA present in neoplastic tissue.
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.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
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).
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.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.
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.
A cell line derived from cultured tumor cells.
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.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
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 introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
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.
An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.
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.
Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)
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 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 strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.
Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
DNA present in neoplastic tissue.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
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.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
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.
The return of a sign, symptom, or disease after a remission.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
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.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
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.
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Immunological rejection of leukemia cells following bone marrow transplantation.
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.
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.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from spontaneous leukemia in AKR strain mice.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
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.
Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.
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)
Tetracyclic spiro-BENZAZEPINES isolated from the seeds of CEPHALOTAXUS. They are esters of the alkaloid cephalotaxine and may be effective as antineoplastic agents.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A general term for various neoplastic diseases of the lymphoid tissue.
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Elements of limited time intervals, contributing to particular results or situations.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A subdiscipline of genetics which deals with the cytological and molecular analysis of the CHROMOSOMES, and location of the GENES on chromosomes, and the movements of chromosomes during the CELL CYCLE.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Increased numbers of platelets in the peripheral blood. (Dorland, 27th ed)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.
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
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 development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
Inorganic or organic compounds that contain arsenic.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multiple myeloma or develop as a terminal complication during the disease.
A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1.
Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.
The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.
An anthracenedione-derived antineoplastic agent.
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.
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 relationship between the dose of an administered drug and the response of the organism to the drug.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A tricyclo bridged hydrocarbon.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
Techniques for the removal of subpopulations of cells (usually residual tumor cells) from the bone marrow ex vivo before it is infused. The purging is achieved by a variety of agents including pharmacologic agents, biophysical agents (laser photoirradiation or radioisotopes) and immunologic agents. Bone marrow purging is used in both autologous and allogeneic BONE MARROW TRANSPLANTATION.
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.
A spontaneous diminution or abatement of a disease over time, without formal treatment.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.
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.
A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Serine-threonine protein kinases that relay signals from CYTOKINE RECEPTORS and are involved in control of CELL GROWTH PROCESSES; CELL DIFFERENTIATION; and APOPTOSIS.
An extramedullary tumor of immature MYELOID CELLS or MYELOBLASTS. Granulocytic sarcoma usually occurs with or follows the onset of ACUTE MYELOID LEUKEMIA.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. EC 2.7.7.31.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A leukemia affecting young children characterized by SPLENOMEGALY, enlarged lymph nodes, rashes, and hemorrhages. Traditionally classed as a myeloproliferative disease, it is now considered a mixed myeloproliferative-mylelodysplastic disorder.
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Proteins prepared by recombinant DNA technology.
Antibodies produced by a single clone of cells.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
Irradiation of the whole body with ionizing or non-ionizing radiation. It is applicable to humans or animals but not to microorganisms.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.

Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins. (1/2847)

Bcr-Abl plays a critical role in the pathogenesis of Philadelphia chromosome-positive leukemia. Although a large number of substrates and interacting proteins of Bcr-Abl have been identified, it remains unclear whether Bcr-Abl assembles multi-protein complexes and if it does where these complexes are within cells. We have investigated the localization of Bcr-Abl in 32D myeloid cells attached to the extracellular matrix. We have found that Bcr-Abl displays a polarized distribution, colocalizing with a subset of filamentous actin at trailing portions of migrating 32D cells, and localizes on the cortical F-actin and on vesicle-like structures in resting 32D cells. Deletion of the actin binding domain of Bcr-Abl (Bcr-AbI-AD) dramatically enhances the localization of Bcr-Abl on the vesicle-like structures. These distinct localization patterns of Bcr-Abl and Bcr-Abl-AD enabled us to examine the localization of Bcr-Abl substrate and interacting proteins in relation to Bcr-Abl. We found that a subset of biochemically defined target proteins of Bcr-Abl redistributed and co-localized with Bcr-Abl on F-actin and on vesicle-like structures. The co-localization of signaling proteins with Bcr-Abl at its sites of localization supports the idea that Bcr-Abl forms a multi-protein signaling complex, while the polarized distribution and vesicle-like localization of Bcr-Abl may play a role in leukemogenesis.  (+info)

Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. (2/2847)

Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility.  (+info)

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation. (3/2847)

Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.  (+info)

Chronic myelogenous leukemia--progress at the M. D. Anderson Cancer Center over the past two decades and future directions: first Emil J Freireich Award Lecture. (4/2847)

The purpose of this study was to review the progress in clinical and translational research in chronic myelogenous leukemia (CML) over the past 20 years at M.D. Anderson Cancer Center. The CML database updating the clinical and basic research investigations was reviewed as the source of this report. Publications resulting from these investigations were summarized. The long-term results with intensive chemotherapy, IFN-alpha therapy alone or in combination, autologous stem cell transplantation, and new agents such as homoharringtonine and decitabine showed encouraging results. Biological studies related to the BCR-ABL molecular abnormality, other molecular events, and the detection of minimal residual disease were detailed. Future strategies with potential promise in CML were outlined. Significant progress in understanding CML biology and in treating patients afflicted with the disease has occurred. Several therapeutic and research tools are currently investigated, which should hopefully improve further the prognosis of patients with CML.  (+info)

Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance. (5/2847)

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)

Presence of P210bcrabl is associated with decreased expression of a beta chemokine C10 gene in a P210bcrabl-positive myeloid leukemia cell line. (6/2847)

BACKGROUND: Chronic myelogenous leukemia (CML) is thought to start with the acquisition of the t(9;22) chromosomal translocation that codes for the P210bcrabl tyrosine-specific protein kinase. The CML cells exhibit anchorage-independent cell growth and genetic instability. After the initial phase, the cells acquire the phenotype of growth factor-independent growth. After the chronic phase, the disease evolves into the accelerated and blastic phases through the process of sequential random mutation. MATERIALS AND METHODS: To identify some of the genetic changes that contribute to the phenotype of blastic and accelerated phase cells, we used differential display PCR to compare levels of cDNA reverse transcripts of mRNA in 32Dc13 cells and 32Dc13 cells that were stably transfected with a bcrabl cDNA plasmid in a constitutively expressed transcription unit. These cells were designated 32Dc13P210bcrabl. For these studies, we used the 32D myeloid leukemia cell line, which depends on IL-3 for growth. RESULTS: Following introduction of the bcr-abl cDNA through transfection, the cell line became growth factor independent, mimicking the change in phenotype that occurs during the later phases of CML. These differential display screening assays detected altered levels of transcripts for 28 genes. Of interest to the biology of growth factor-independent growth in the bcrabl-positive 32D cells was the fact that the C10 beta chemokine gene was expressed at higher levels in the 32Dc13 cells than in the 32Dc13P210bcrabl cells. CONCLUSIONS: These studies show that a C10 beta chemokine gene was expressed at different levels with or without P210bcrabl.  (+info)

Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion. (7/2847)

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.  (+info)

Extremely high and specific activity of DNA enzymes in cells with a Philadelphia chromosome. (8/2847)

BACKGROUND: Chronic myelogenous leukemia (CML) results from chromosome 22 translocations (the Philadelphia chromosome) that creates BCR-ABL fusion genes, which encode two abnormal mRNAs (b3a2 and b2a2). Various attempts to design antisense oligonucleotides that specifically cleave abnormal L6 BCR-ABL fusion mRNA have not been successful. Because b2a2 mRNA cannot be effectively cleaved by hammerhead ribozymes near the BCR-ABL junction, it has proved very difficult to engineer specific cleavage of this chimeric mRNA. Nonspecific effects associated with using antisense molecules make the use of such antisense molecules questionable. RESULTS: The usefulness of DNA enzymes in specifically suppressing expression of L6 BCR-ABL mRNA in mammalian cells is demonstrated. Although the efficacy of DNA enzymes with natural linkages decreased 12 hours after transfection, partially modified DNA enzymes, with either phosphorothioate or 2'-O-methyl groups at both their 5' and 3' ends, remained active for much longer times in mammalian cells. Moreover, the DNA enzyme with only 2'-O-methyl modifications was also highly specific for abnormal mRNA. CONCLUSIONS: DNA enzymes with 2'-O-methyl modifications are potentially useful as gene-inactivating agents in the treatment of diseases such as CML. In contrast to conventional antisense DNAs, some of the DNA enzymes used in this study were highly specific and cleaved only abnormal BCR-ABL mRNA.  (+info)

TY - JOUR. T1 - Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib. AU - Cortes, Jorge E.. AU - Jean Khoury, H.. AU - Kantarjian, Hagop. AU - Brümmendorf, Tim H.. AU - Mauro, Michael J.. AU - Matczak, Ewa. AU - Pavlov, Dmitri. AU - Aguiar, Jean M.. AU - Fly, Kolette D.. AU - Dimitrov, Svetoslav. AU - Leip, Eric. AU - Shapiro, Mark. AU - Lipton, Jeff H.. AU - Durand, Jean Bernard. AU - Gambacorti-Passerini, Carlo. PY - 2016/6/1. Y1 - 2016/6/1. N2 - Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N=570) ...
Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt ...
Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt ...
The added value of 2nd generation tyrosine kinase inhibitors (TKIs) is currently perhaps the most-discussed issue in chronic myeloid leukemia (CML) research and treatment. Therefore, with their recently published article Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed, Ibrahim et al.1 focussed on an important topic. However, in our opinion, the methodological approach used in this paper is not always appropriate.. The choice of the historical control group treated with interferon-alfa seems not to be optimal. Even before the imatinib era, progress had been made in the treatment of CML as the results of the consecutive German studies and of the French CML-study group show.2-4 We doubt that the results of the 20-year old MRC trial represent an appropriate comparator group for the results achieved by the use of 2nd generation tyrosine kinase inhibitors. Furthermore, the authors use two different ...
TY - JOUR. T1 - Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210(bcr-abl) tyrosine kinase activity. AU - Schwartz, Gretchen N.. AU - Liu, Yue Qin. AU - Tisdale, John. AU - Walshe, Kate. AU - Fowler, Daniel. AU - Gress, Ronald. AU - Bergan, Raymond C.. PY - 1998/1/1. Y1 - 1998/1/1. N2 - p210(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67% ± 19% (mean ± SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also ...
TY - JOUR. T1 - Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. AU - OHare, Thomas. AU - Deininger, Michael W.N.. AU - Eide, Christopher A.. AU - Clackson, Tim. AU - Druker, Brian J.. PY - 2011/1/15. Y1 - 2011/1/15. N2 - Beginning with imatinib a decade ago, therapy based on targeted inhibition of the BCR-ABL kinase has greatly improved the prognosis for chronic myeloid leukemia (CML) patients. The recognition that some patients experience relapse due to resistance-conferring point mutations within BCR-ABL sparked the development of the second-generation ABL kinase inhibitors nilotinib and dasatinib. Collectively, these drugs target most resistant BCR-ABL mutants, with the exception of BCR-ABLT315I. A third wave of advances is now cresting in the form of ABL kinase inhibitors whose target profile encompasses BCR-ABLT315I. The leading third-generation clinical candidate for treatment-refractory CML, including patients with the T315I ...
Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow - the spongy tissue inside bones where blood cells are made. CML causes an increased number of white blood cells in the blood.. The term chronic in chronic myelogenous leukemia indicates that this cancer tends to progress more slowly than acute forms of leukemia. The term myelogenous (my-uh-LOHJ-uh-nus) in chronic myelogenous leukemia refers to the type of cells affected by this cancer.. Chronic myelogenous leukemia can also be called chronic myeloid leukemia and chronic granulocytic leukemia. It typically affects older adults and rarely occurs in children, though it can occur at any age.. Advances in treatment have contributed to a greatly improved prognosis for people with chronic myelogenous leukemia. Most people will achieve remission and live for many years after diagnosis. ...
A phase of chronic myelogenous leukemia in which the disease is progressing. In this phase, 10% to 19% of the cells in the blood and bone marrow are blast cells (immature blood cells).
TY - JOUR. T1 - Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia. AU - Quintás-Cardama, Alfonso. AU - Cortes, Jorge. PY - 2008/7/15. Y1 - 2008/7/15. N2 - Despite the efficacy of imatinib therapy in chronic myelogenous leukemia, the development of resistance continues to challenge the treatment of this disease. Mutations within the kinase domain of BCR-ABL1 constitute the most frequent mechanism of resistance in patients with chronic myelogenous leukemia treated with imatinib or the second generation tyrosine kinase inhibitors nilotinib and dasatinib. Of particular concern is the substitution of the threonine residue at the highly conserved gatekeeper residue 315 with a bulkier hydrophobic isoleucine amino acid. This mutation causes steric hindrance precluding the access ATP-competitive inhibitors to the ATP-binding pocket. To expedite the identification of strategies to override the resistance imposed by the T3151 mutation, several strategies have been pursued, ...
RATIONALE: Vaccines made from gene-modified cancer cells may help the body build an effective immune response to kill cancer cells. Imatinib mesylate ma
TY - JOUR. T1 - Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia without hitting leukemic stem cells. AU - Lenaerts, Tom. AU - Pacheco, Jorge M.. AU - Traulsen, Arne. AU - Dingli, David M. PY - 2010/6. Y1 - 2010/6. N2 - Background: Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia - regardless of the significant reduction of disease burden during treatment - since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited. Design and Methods: We studied the natural history of a large cohort of virtual patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy using a computational model of hematopoiesis and chronic myeloid leukemia that takes into account stochastic dynamics within the hematopoietic stem and early progenitor cell pool. Results: We found that in the overwhelming majority of patients ...
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing ...
Title: Interferon alpha for Treatment of Chronic Myeloid Leukemia. VOLUME: 12 ISSUE: 3. Author(s):Bengt Simonsson, Henrik Hjorth-Hansen, Ole Weis Bjerrum and Kimmo Porkka. Affiliation:Department of Hematology 50C, Uppsala University Hospital, Uppsala, 75185 Sweden.. Keywords:Interferon-alpha, chronic myeloid leukemia, imatinib, combination therapy, chronic myeloid leukemia stem cells, BCR, BCR-ABL1, CML cell, fluorescent in situ hybridization, allogeneic stem cell transplantation, allogeneic SCT, poietic stern cells, leukemic effect in CML, psychosis, autoimmune disorders, thyreoiditis. Abstract: Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. > 2 log tumor mass reduction). IFN-α was then recommended as first line medical treatment until ...
We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative ...
TY - JOUR. T1 - Prominent hematogone hyperplasia in BCR-ABL1-positive chronic myelogenous leukemia. T2 - Mimicking recurrent B-lymphoid blast crisis. AU - Horna, Pedro. AU - Pantazopoulos, Panagiotis. AU - Lancet, Jeffrey E.. AU - Moscinski, Lynn C.. AU - Zhang, Ling. PY - 2014/8. Y1 - 2014/8. UR - http://www.scopus.com/inward/record.url?scp=84904886239&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84904886239&partnerID=8YFLogxK. U2 - 10.3109/10428194.2013.869330. DO - 10.3109/10428194.2013.869330. M3 - Letter. C2 - 24304373. AN - SCOPUS:84904886239. VL - 55. SP - 1952. EP - 1954. JO - Leukemia and Lymphoma. JF - Leukemia and Lymphoma. SN - 1042-8194. IS - 8. ER - ...
The BCR-ABL1 oncoprotein is found in a subset of patients with ALL carrying the Philadelphia chromosome. This translocation is the most common cytogenetic abnormality in adults, with ALL occurring in 25% of patients (33). BCR-ABL1 defines a high-risk group and, as such, patients receive intensive chemotherapy in combination with ABL TKIs and are considered for hematopoietic stem cell transplantation (HSCT). Despite the great success with combination of high-dose ABL TKIs and intensive chemotherapy, there are still drawbacks that need to be addressed. Above all, 40% of patients, even with HSCT, have relapse of the disease. Furthermore, it is not clear whether responsive patients without HSCT cannot have relapse of the disease, as there is evidence that BCR-ABL1-positive leukemia stem cells remain present in the patients bone marrow even after years of therapy. Therefore, it is necessary to define targets in BCR-ABL1-positive leukemia stem cells that may be candidates for new treatment ...
Read about the report that tyrosine kinase inhibitors therapy is relatively safe for kidney function in chronic myeloid leukemia patients.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The significance of molecular response depth is not well defined in patients with chronic phase chronic myeloid leukemia (CP-CML) under imatinib treatment. We retrospectively evaluated clinical records of 178 patients with CP-CML. Eighty-eight patients achieved complete molecular response during long term follow-up. Our results implicate that deeper molecular response is associated with improvement in disease outcome and a slight prolongation in progression-free survival. ...
Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TIC). This discovery has led to the cancer stem cell hierarchy concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the pathophysiology of these diseases has provided interesting insights into not only the hierarchy of leukemia stem cells but also their clonal evolution. Both shared and unique regulatory mechanisms affecting normal and CML stem ...
Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but the persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate the expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling, and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN ...
The FDA has approved bosutinib (Bosulif) to treat chronic myelogenous leukemia (CML). The drug is intended for patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who are resistant to or who cannot tolerate other therapies, including imatinib (Gleevec).. The safety and effectiveness of Bosulif was evaluated in a single clinical trial that enrolled 546 adult patients with chronic, accelerated, or blast phase CML. All patients had disease that progressed after treatment with imatinib or imatinib followed by dasatinib (Sprycel) and/or nilotinib (Tasigna), or who could not tolerate the side effects of prior therapy.. Results showed 34% of patients with chronic phase CML who had been previously treated with imatinib achieved a major cytogenetic response after 24 weeks. Of the patients who achieved a major cytogenetic response at any time, 52.8% had their response last at least 18 months. Among patients previously treated with imatinib followed by dasatinib and/or ...
Clinical trial for Chronic myeloid leukemia , Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...
Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN has ...
In this retrospective analysis, fourteen/18 (78%) evaluable patients were found challenged with higher doses of IM (600-800 mg/day), with one return to CP and one transient CCyR after IM combined with chemotherapy, and 12 failures. Six patients (1 CP, 5 BC) were treated with dasatinib, and no difference in survival was seen between dasatinib-treated and non-treated patients (p=0.15). None of the patients received nilotinib. Additionally, 3 patients underwent allogeneic stem cell transplantation with 2 remaining alive at 1 and 14 months follow-up. Finally, at latest follow-up, overall survival since IM initiation (Figure 1B), however longer for CP (42.5 Mo.) was not statistically different than that for AP+BC (17.5 Mo., p=0.08) patients.. The onset of BCR-ABLT315I mutations during the treatment of CML with TKIs remains challenging, because this mutation is the most frequently identified in IM-treated patients6, and none of the TKIs clinically available to date4,5,6 retain any activity in vitro. ...
Tasigna (nilotinib) is approved in more than 122 countries for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant or intolerant to at least one prior therapy, including Glivec (imatinib), and in more than 110 countries for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase. Tasigna is approved in the European Union (EU) for the treatment of Ph+ CML in the chronic phase in pediatric patients with resistance or intolerance to prior therapy including Glivec and for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase.. IMPORTANT SAFETY INFORMATION for TASIGNA® (nilotinib) Capsules Use with caution in patients with uncontrolled or significant cardiac disease and in patients who have or may develop prolongation of QTc. Low levels of potassium or magnesium must be corrected prior to Tasigna administration. Monitor closely for an effect on ...
The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5′ part of the BCR gene on chromosome 22 to the 3′ part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors. This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18), loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found. We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18)], resulting to Glivec resistance but good response to nilotinib. The dic(17;18) might be a marker for poor prognosis
53 NCCN Guidelines for Patients ® : Chronic Myeloid Leukemia, 2018 Acronyms Acronyms ALL acute lymphoblastic leukemia AML acute myeloid leukemia CAM complementary and alternative medicine CBC complete blood count CCyR complete cytogenetic response CBC complete blood count CML chronic myeloid leukemia CMR complete molecular response DLI donor lymphocyte infusion DNA deoxyribonucleic acid EMR early molecular response FDA Food and Drug Administration FISH fluorescence in situ hybridization GVL graft-versus-leukemia HCT hematopoietic cell transplant HLA human leukocyte antigen IS International Scale NCCN National Comprehensive Cancer Network MMR major molecular response MPN myeloproliferative neoplasm QPCR quantitative reverse transcriptase-polymerase chain reaction TKI tyrosine kinase inhibitor ...
For hematologic toxicity, treatment should be withheld for an absolute neutrophil count , 1,000 × 106/L or platelets , 50,000 × 106/L until levels increase above these thresholds. Treatment can be resumed at the same dose if recovery occurs within 2 weeks and at a dose reduced by 100 mg if recovery takes , 2 weeks. If cytopenia recurs, the dose should be reduced by an additional 100 mg when restarting treatment after recovery.. Concomitant use of bosutinib with strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin), moderate CYP3A inhibitors (eg, erythromycin, fluconazole, diltiazem), or strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin) should be avoided. Short-acting antacids or H2 blockers should be used as an alternative to proton pump inhibitors.. Safety Profile IN THE TOTAL population of the phase III trial, the most common adverse events of any grade in the bosutinib group were diarrhea (70% vs 34% in imatinib group), nausea (35% vs 38%), thrombocytopenia ...
abstract = In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN+HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN+HU reduced the percentage of Ph-positive metaphases in 56{\%} of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88{\%} had a Ph ...
article{801ae827-4c64-4154-8fc7-42929426f3d8, abstract = {In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN+HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN+HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive ...
There are several treatments used for blast phase chronic myelogenous leukemia. Learn about treatments that may be offered to treat blast phase CML.
The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML.. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML.. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML.. CITATION Mol Cancer. 2009 Sep 1;8:69. ...
Semantic Scholar extracted view of Dasatinib-induced pulmonary hypertension in chronic myelogenous leukaemia. by Seongseok Yun et al.
K-562 Cell Slide (Human (53yrs, Female) bone marrow, chronic myelogenous leukemia (CML)) (5 slides/pk) Slide for ICC HCLS-17004 K-562 Cell Slide (Human (53yrs, Female) bone marrow, chronic myelogenous leukemia (CML)) (5 slides/pk) Slide for ICC HCLS-17004
Chronic myelogenous leukemia treatments include tyrosine kinase inhibitors, high-dose therapy with allogeneic transplantation, and other medications. Get detailed information about chronic myelogenous leukemia (CML) treatment options in this summary for clinicians.
The US Food and Drug Administration (FDA) has approved Bosulif (bosutinib) to treat adults with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).Indications: Bosulif is a kinase inhibitor indicated for the treatment of adult patients with newly-diagnosed chronic phase Ph+ CML.Dosage and administration: 400 mg orally once daily with food.
Chronic myeloid leukaemia. Light micrograph of blood cells from bone marrow in a case of chronic myeloid leukaemia. Leukaemia is a cancer where certain blood cells form in excess. There are several chronic forms, classified according to the type of cell affected. Chronic myeloid leukaemia is a cancer affecting the myeloid tissue (bone marrow), specifically the white blood cell precursors (myeloblasts) that form a type of white blood cell known as granulocytes. The pink cells are precursor or white blood cells. The pale orange ones are red bloods cells. Magnification: x1000 when printed at 10 centimetres across. - Stock Image C015/1835
Hematology: Chronic myelogenous leukemia (cml) | Stem cell transplant. Treatment in Ulm, Germany ✈ Find the best medical programs at BookingHealth - ✔Compare the prices ✔Online booking.
Imatinib became the front-line treatment for patients with chronic-phase chronic myelogenous leukemia (CP-CML) based on results from the International Randomized Study of Interferon and STI571 (IRIS), which compared imatinib versus interferon-α combined with low-dose cytarabine.1 According to the 5-year follow-up of the IRIS trial, imatinib used as initial therapy produced a cumulative complete cytogenetic response (CCyR) rate of 87%.1,2 The 8-year follow-up, presented in abstract form only, revealed estimated overall and event-free survivals of 85% and 81%, respectively.3 Patients receiving imatinib have also reported improved health-related quality of life.4 However, approximately 30% of the patients develop resistance and/or intolerance to imatinib.5 The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib have increased potency compared with imatinib.6,7 They were approved initially for patients in whom imatinib had failed, and subsequently for front-line treatment of ...
TY - JOUR. T1 - Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice. T2 - Identification of risk factors and the role of prophylaxis. AU - Caocci, Giovanni. AU - Mulas, Olga. AU - Annunziata, Mario. AU - Luciano, Luigiana. AU - Bonifacio, Massimiliano. AU - Orlandi, Ester Maria. AU - Pregno, Patrizia. AU - Galimberti, Sara. AU - Russo Rossi, Antonella. AU - Abruzzese, Elisabetta. AU - Iurlo, Alessandra. AU - Martino, Bruno. AU - Sgherza, Nicola. AU - Binotto, Gianni. AU - Castagnetti, Fausto. AU - Gozzini, Antonella. AU - Fozza, Claudio. AU - Bocchia, Monica. AU - Sicuranza, Anna. AU - Stagno, Fabio. AU - Efficace, Fabio. AU - Usala, Emilio. AU - De Gregorio, Fiorenza. AU - Scaffidi, Luigi. AU - Elena, Chiara. AU - Pirillo, Francesca. AU - Baratè, Claudia. AU - Trawinska, Malgorzata Monika. AU - Cattaneo, Daniele. AU - Labate, Claudia. AU - Gugliotta, Gabriele. AU - Molica, Matteo. AU - Specchia, ...
Detection of Human IRAK2 by Western Blot. Western blot shows lysates of Jurkat human acute T cell leukemia cell line, Raji human Burkitts lymphoma cell line, K562 human chronic myelogenous leukemia cell line, and HeLa human cervical epithelial carcinoma cell line. PVDF Membrane was probed with 0.5 µg/mL of Human IRAK2 Monoclonal Antibody (Catalog # MAB6690) followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007). A specific band was detected for IRAK2 at approximately 65 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1 ...
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 ...
TY - JOUR. T1 - Immunophenotypic and genotypic characteristics of chronic myelogenous leukemia in blast crisis. AU - Yen, C. C.. AU - Liu, J. H.. AU - Wang, W. S.. AU - Fan, F. S.. AU - Chiou, T. J.. AU - Tai, C. J.. AU - Yang, M. H.. AU - Chao, T. C.. AU - Hsiao, L. T.. AU - Chen, P. M.. PY - 2000. Y1 - 2000. N2 - Background. Chronic myelogenous leukemia (CML) may transform into blast crisis (BC) if not properly treated. Among patients with transformation, 20% to 30% will develop BC with lymphoid-associated antigens (Ly-BC), and the remaining cases with myeloid-associated antigens (My-BC) or with both (Mix-BC). In this study, we investigated the lineage of blast cells in CML-BC using immunophenotypic and genetic analyses and analyzed the prognostic significance of genotypic change in CML-BC. Methods. Twenty-one patients with CML-BC diagnosed at the Taipei Veterans General Hospital from 1982 to 1992 were included. Immunophenotyping was done by using the avidin-biotin immunoperoxidase technique. ...
BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial ...
TY - JOUR. T1 - Blastic Mantle Cell Lymphoma Developing Concurrently in a Patient with Chronic Myelogenous Leukemia and a Review of the Literature. AU - Rodler, Eve. AU - Welborn, Jeanna L. AU - Hatcher, Sandra. AU - Unger, Katherine. AU - Larkin, Edward. AU - Gumerlock, Paul H.. AU - Wun, Theodore. AU - Richman, Carol M. PY - 2004/4. Y1 - 2004/4. N2 - Non-Hodgkins lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3-year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. Fluorescence in situ hybridization (FISH) of the bone marrow revealed ...
Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients / Alti kronik miyeloid losemi olgusunda farkli kirik noktali varyant Philadelphia translokasyonlari.
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 ...
Comment: Management of De Novo Chronic Myelogenous Leukemia and Imatinib-Induced Acute Rhabdomyolysis With the Second-Generation Tyrosine Kinase Inhibitor ...
Celecoxib is a selective COX-2 inhibitor and its anti-tumor effect has been reported in various cancers [7-9]. In this paper, we demonstrated that the anti-tumor activities of celecoxib included cell cycle arrest, necrosis, apoptosis and autophagy suppression in KBM5 and KBM5-T315I cells. KBM5-T315I cell is a mutation line of KBM5 with a threonine to isoleucine mutation at position 315 in the Abl fragment of the Bcr-Abl kinase domain. This leads to an alteration of the enzymes active site and makes these cells resistant to the first and second generation of TKI [35]. Results showed that celecoxib caused cytotoxic effect in the two CML cell lines which was dose and time-dependent. When extending the celecoxib incubation time, the inhibition effect was stronger in KBM5-T315I cells than in KBM5 cells (Fig. 1), indicating that celecoxib might be used as a new therapeutic agents in imatinib-resistant CML. In accordance with other reports [19, 21], our findings also confirmed that the anti-tumor ...
Title: Molecular Pathogenesis of Philadelphia-Positive Chronic Myeloid Leukemia - is it all BCR-ABL?. VOLUME: 11 ISSUE: 1. Author(s):H. Rumpold and G. Webersinke. Affiliation:Department of Haematology and Medical Oncology, Hospital Barmherzige Schwestern Linz, Seilerstaette 4, 4010 Linz, Austria.. Keywords:BCR-ABL, CML, pathogenesis, molecular genetics, chronic myeloproliferative diseases, Chronic Myelogenous Leukemia, Leukemia, Mastocytosis, diagnostic, chromosome, oncogen, stem cells, MOLECULAR BIOLOGY, cytoplasm, tyrosine kinase, plekstrine homology domain, toxin substrate, phosphorylation of tyrosine, immune system, bone marrow cells, haematopoiesis, pulmonary haemorrhages, PH-TRANSLOCATION, risk factor, phenotype, heterozygous, myeloproliferative nepolasms, myeloid colony, phenylalanine, leukemic cell, cell, phosphorylation, antiapoptotic protein, michochondrial cytochrome-c, mRNA, disease progression, Granulocytemacrophage progenitor cells, mutation rate, clonogenicity potential, STEM ...
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.
TY - JOUR. T1 - DETECTION OF REARRANGEMENT WITHIN THE BREAKPOINT CLUSTER REGION OF CHROMOSOME 22 IN THE DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA. AU - HUTCHINS, C.. AU - CASEY, G.. AU - White, Deborah. AU - MOORE, S.. AU - RUDZKI, Z.. AU - KIMBER, R.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Chronic myeloid leukemia (CML) is characterised by the presence of a Philadelphia (Ph) chromosome in approximately 95% of patients. Molecular analysis has shown that the Ph chromosome translocation breakpoints are clustered within 5.8kb on chromosome 22 (breakpoint cluster region or bcr). This has facilitated the diagnosis of CML by nucleic acid hybridisation using probes specific for the bcr to detect DNA rearrangement in this region. Forty patients diagnosed with CML, including four with variant Ph chromosome translocations and three with normal karyotypes were analysed for rearrangement within the bcr. All except one patient with Ph negative CML had rearrangement within the bcr. In contrast, none of the patients ...
This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute L
Targeting Mitochondrial Oxidative Phosphorylation Eradicates Therapy-Resistant Chronic Myeloid Leukemia Stem Cells Scientists performed metabolic analyses on both stem cell-enriched and differentiated cells derived from individuals with chronic myeloid leukemia (CML), and they compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, they demonstrated that primitive CML cells rely on upregulated oxidative metabolism for their survival. [Nat Med] Abstract Induction of Cancer Cell Stemness by Depletion of Macrohistone H2A1 in Hepatocellular Carcinoma Using hepatocellular carcinomas cell lines researchers found that shRNA-mediated macroH2A1 knock-down induces acquisition of cancer stem cells-like features, including the growth of significantly larger and less-differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to ...
TY - JOUR. T1 - Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE). AU - Do, Young Rok. AU - Kwak, Jae Yong. AU - Kim, Jeong A.. AU - Kim, Hyeoung Joon. AU - Chung, Joo Seop. AU - Shin, Ho Jin. AU - Kim, Sung Hyun. AU - Bunworasate, Udomsak. AU - Choi, Chul Won. AU - Zang, Dae Young. AU - Oh, Suk Joong. AU - Jootar, Saengsuree. AU - Reksodiputro, Ary Harryanto. AU - Lee, Won Sik. AU - Mun, Yeung Chul. AU - Kong, Jee Hyun. AU - Caguioa, Priscilla B.. AU - Kim, Hawk. AU - Park, Jinny. AU - Kim, Dong Wook. PY - 2020/1/1. Y1 - 2020/1/1. N2 - In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice-daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once-daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months follow-up, MMR was higher with ...
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 ...
Targeted drugs are the initial treatment for most people diagnosed with chronic myelogenous leukemia. If the disease doesnt respond or becomes resistant to the first targeted drug, doctors may consider other targeted drugs, such as omacetaxine (Synribo), or other treatments. Side effects of these targeted drugs include swelling or puffiness of the skin, nausea, muscle cramps, rash, fatigue, diarrhea, and skin rashes.. Doctors havent determined a safe point at which people with chronic myelogenous leukemia can stop taking targeted drugs. For this reason, most people continue to take targeted drugs even when blood tests reveal a remission of chronic myelogenous leukemia.. Blood stem cell transplant. A blood stem cell transplant, also called a bone marrow transplant, offers the only chance for a definitive cure for chronic myelogenous leukemia. However, its usually reserved for people who havent been helped by other treatments because blood stem cell transplants have risks and carry a high rate ...
Thromboembolic events are common cause of death in patients with myeloproliferative disorders (MPD) especially those with cardiac involvement . In previous studies, cardiac involvement, including coronary arterial thrombosis, myocardial infarction, pulmonary hypertension (PHT), asymptomatic pericardial effusion, cardiac tamponade, intractable cardiac failure due to intraventricular thrombosis, and stenosis of aortic, mitral valves, even requiring surgical treatment had been reported in MPD This cohort study was carried out in three Iraqi teaching hospitals for Medicine including Al-Kadhimyya Teachginmg Hospital , Al-Yarmook Teaching Hospital (including National haematology Centre) and Merjan Teaching hospital in Babylon. The study groups were 26 patients (mean age female and male) with MPD and 30 age-matched healthy controls. MPD group included sixteen cases chronic phase chronic myelogenous leukemia (CML), two idiopathic myelofibrosis (MF) , seven polcythemia vera and one essential ...
Williams LA, Ault P, Garcia-Gonzalez A, et al. Relationship of patient-reported symptoms to daily functioning in chronic myeloid leukemia [abstract]. American Society of Hematology 54th Annual Meeting and Exposition, Atlanta GA, Dec 8-11, 2012. Blood 118(21): 2012; 4260.. Williams LA, Jacobsen PB, Sailors MH, et al. Symptoms in chronic myeloid leukemia survivors on tyrosine kinase inhibitor therapy at two cancer centers [abstract]. Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2012 International Symposium on Supportive Care in Cancer, New York NY, Jun 28-30, 2012. Support Care Cancer 20(Suppl 1): S240, 2012; 1003.. Garcia-Gonzalez A, Ault P, Williams LA, Williams JL, Cleeland CS, Cortes JE. Interactive voice response system compliance in chronic myeloid leukemia population [abstract]. American Society of Clinical Oncology 48th Annual Meeting, Chicago IL, Jun 1-5, 2012; e19589.. Williams LA, Ault PS, Garcia-Gonzalez A, et al. ...
Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review.Environ Health Perspect. 2007;115(1):138-145.. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.Sci Transl Med. 2013;5(177):177ra38.. Campana D, Pui C-H. Childhood Leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloffs Clinical Oncology. 5th ed. Elsevier Saunders; 2013:1849-1872.e11.. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075-2088.. Diller L. Clinical practice. Adult primary care after childhood acute lymphoblastic leukemia.N Engl J Med. 2011;365(15):1417-1424.. Faderl S, OBrien S, Pui CH, et al. Adult acute lymphoblastic leukemia: concepts and strategies.Cancer. 2010;116(5):1165-1176.. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T ...
We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host ...
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 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 ...
Novartis AGs Tasigna, for children one year of age or older with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase, or Ph+ CML-CP. The drug is already approved to treat adults and children with Ph+ CML-CP resistant or intolerant to prior tyrosine kinase inhibitor therapy and prior therapy.. * Orthofix International NVs G-Beam fusion beaming system, for Charcot foot. The company received 510(k) clearance.. * Sun Pharmaceutical Industries Ltd.s Ilumya, for moderate to severe plaque psoriasis.. * Seattle Genetics Inc.s Adcetris-chemotherapy combination, for adults with previously untreated stage 3 or 4 classical Hodgkin lymphoma. The drug is already approved to treat three other types of lymphoma as well as certain patients with mycosis fungoides. Seattle Genetics is developing Adcetris with Takeda Pharmaceutical Co. Ltd.. * Restoration Robotics Inc.s Artas hair transplantation system, for pattern baldness. The company received 510(k) ...
We report a 34 year old man who developed bilateral ptosis and predominantly respiratory, truncal and bulbar weakness, and a high titer of anti acetylcholine receptor antibodies along with a diagnosis of Philadelphia chromosome positive Chronic Myeloid Leukemia (CML). The temporal relationship suggests a possible association.. ...
allogeneic stem cell transplant is the only potential cure for chronic myelogenous leukemia (cml). the procedure is usually done if youre young and dont have any medical issues besides cml.
"Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia". Oncogene. 13 (2): 247-54. PMID ... "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nat. Med. 2 (5): 561-6. ... Different inhibitors have been designed to target different kinases: inhibition of BCR/ABl constitutes the basis of the ... Leukemia. 23 (8): 1441-5. doi:10.1038/leu.2009.50. PMID 19295546. Behbod F, Nagy ZS, Stepkowski SM, Karras J, Johnson CR, ...
Drugs known as tyrosine kinase inhibitors target BCR-ABL, and are the standard treatment for chronic myelogenous leukemia. ... Thus, trastuzumab has been a standard-of-care treatment in both metastatic and early stage HER2-positive breast cancer cases. ... However, after imatinib was used as the first-line therapy, several BCR-ABL-dependent and BCR-ABL-independent mechanisms of ... The majority of chronic myelogenous leukemia cases are caused by a rearrangement between chromosomes 9 and 22. This results in ...
A metaphase cell positive for the bcr/abl rearrangement (associated with chronic myelogenous leukemia) using FISH. The ... chronic myelogenous leukemia, acute lymphoblastic leukemia, Cri-du-chat, Velocardiofacial syndrome, and Down syndrome. FISH on ... An example is the detection of BCR/ABL translocations, where the secondary color indicates disease. This variation is often ... such as translocations and inversions which are hallmark aberrations seen in many types of leukemia and lymphoma. ...
"Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome", Blood, 45 (3): 321-34, PMID 163658 Drexler ... presumably due to the downregulation of surface adhesion molecules by bcr:abl. However, another study suggests that bcr:abl ... The cells are non-adherent and rounded, are positive for the bcr:abl fusion gene, and bear some proteomic resemblance to both ... K562 cells are of the erythroleukemia type, and the cell line is derived from a 53-year-old female chronic myelogenous leukemia ...
... designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosome-positive leukemias ( ... chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous ... an antiviral drug 5-HT3 antagonists Acetylcholine receptor agonists Angiotensin receptor antagonists Bcr-Abl tyrosine-kinase ...
"Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia". Oncogene. 13 (2): 247-54. PMID ... "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nat. Med. 2 (5): 561-6. ... inhibition of BCR/ABl constitutes the basis of the functioning of drugs like imatinib[7] ... "A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo". Blood. 99 (11): 3885-91. doi: ...
Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia". N. Engl. J. Med. 357 (3): 258- ... and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome-positive (Ph+), certain types of gastrointestinal stromal ... In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of abl with bcr (breakpoint cluster ... "Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase". Nat. Med. ...
... is a small molecule BCR-ABL and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia. ... "Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia". 5 Sep 2012. "Bosulif : ... in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib ... October 2012). "Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA ...
"Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL ... chromosome-positive (Ph+) cells at diagnosis, including so-called major route abnormalities (a second Ph chromosome, trisomy 8 ... Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form ... Chronic Myeloid Leukemia at American Cancer Society CML information from The Leukemia & Lymphoma Society Chronic Myelocytic ...
... , sold under the brand name Tasigna, is a medication used to treat chronic myelogenous leukemia (CML) which has the ... It is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity and proliferation of Bcr-Abl ... Nilotinib is used to treat Philadelphia chromosome (Ph+)-positive chronic myelogenous leukaemia. Nilotinib has a number of ... "FDA Approves Tasigna for Treatment of Philadelphia Chromosome Positive Chronic Myeloid Leukemia". U.S. Food and Drug ...
BCR-ABL (Chronic Myeloid Leukemia), BRCA1 / BRCA2 (Breast/Ovarian Cancer), BRAF V600E (Melanoma/Colorectal Cancer), CA-125 ( ... BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia". Blood. 117 ... For instance, in the 1960s, researchers discovered the majority of patients with chronic myelogenous leukemia possessed a ... For many years, the BCR-ABL was simply used as a biomarker to stratify a certain subtype of leukemia. However, drug developers ...
... are a chronic myelogenous leukemia (CML) cell line used for biomedical research. Like all cancer cell lines, it is ... Like other CML cells lines (e.g., K562) KBM-7 cells are positive for the Philadelphia chromosome harboring the BCR-ABL ... "Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line ... KBM-7 cells were derived from a 39-year-old man with chronic myeloid leukemia in blast crisis. The original cell line contained ...
... is used to treat people with chronic myeloid leukemia and people with acute lymphoblastic leukemia who are positive ... It is a tyrosine-kinase inhibitor and works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family ... and adults with newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase ... chronic myeloid leukemia (CML) in the chronic phase. Approval was based on data from 97 pediatric participants with chronic ...
... induction of apoptosis in Philadelphia chromosome-positive chronic myelogenous leukemia cells by an inhibitor of BCR-ABL ... Burke, B.A.; Carroll, M. (2010). "BCR-ABL: A multi-faceted promoter of DNA mutation in chronic myelogeneous leukemia". Leukemia ... Nimmanapalli, R.; Bhalla, K. (2002). "Novel targeted therapies for Bcr-Abl positive acute leukemias: Beyond STI571". Oncogene. ... "Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia". British Journal of ...
... s (TKI) are the first-line therapy for most patients with chronic myelogenous leukemia (CML). ... "BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review". ... Bcr-Abl dependent mechanisms include over expression or amplification of the Bcr-Abl gene and point mutations within the Bcr- ... Bcr) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that ...
... a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The BCR-ABL ... "Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines". Int. J. Hematol. 65 (2 ... Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to ... "Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr". Cancer Res. 63 (2): 298-303. PMID 12543778. ...
"Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nat Med. 2 (5): 561-6. ... Based on this work imatinib was developed against chronic myelogenous leukemia (CML) and later gefitinib and erlotinib aiming ... For example, they have substantially improved outcomes in chronic myelogenous leukemia. They are also called tyrphostins, the ... Bcr-Abl tyrosine-kinase inhibitor Protein kinase inhibitor Yaish P, Gazit A, Gilon C, Levitzki A (1988). "Blocking of EGF- ...
... a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based ... Subsequent studies of 449 patients treated during 4 years with ponatinib for chronic phase chronic myelogenous leukemia found ... Approval was also granted for T315I-positive and T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia. ... Experts in Chronic Myeloid Leukemia (May 2013). "The price of drugs for chronic myeloid leukemia (CML) is a reflection of the ...
"Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia". New England Journal of ... "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nature Medicine. 2 (5): ... a drug that has saved the lives of thousands of patients with chronic myelogenous leukaemia (CML) and gastrointestinal stromal ... a selective BCR-ABL inhibitor for the treatment of chronic myeloid leukaemia (CML), which converted a fatal cancer into a ...
... designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosome-positive leukemias ( ... chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous ...
1989). "Structural alterations of the BCR and ABL genes in Ph1 positive acute leukemias with rearrangements in the BCR gene ... in the human c-abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia". Mol ... "A novel variant of the bcr-abl fusion product in Philadelphia chromosome-positive acute lymphoblastic leukemia". Leukemia. 4 (6 ... 1987). "The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript". Mol. ...
BCR/ABL positive)/(Ph1 positive)/t(9;22)(q34;q11) M9876/3 Atypical chronic myelogenous leukemia BCR/ABL negative Atypical ... NOS M9875/3 Chronic myelogenous leukemia BCR/ABL positive Philadelphia chromosome (Ph1 positive) t(9;22)(q34;q11) Chronic ... NOS Chronic myelogenous leukemia, NOS Chronic granulocytic leukemia, NOS Chronic myelocytic leukemia, NOS M9866/3 Acute ... Chronic lymphocytic leukemia Chronic lymphoid leukemia Chronic lymphatic leukemia M9826/3 Burkitt cell Leukemia (see also M9687 ...
... chronic myeloid leukemia (CML) is comparable to acute myeloid leukemia M2 because it also forms a fusion oncoprotein - BCR-Abl ... The acute myeloid leukemia Kasumi-1 cell line was selected for the experiment due to its AML1-ETO positive characteristics. ... Chi Y, Lindgren V, Quigley S, Gaitonde S (2008). "Acute Myelogenous Leukemia With t(6;9)(p23;q34) and Marrow Basophilia: An ... has had a tremendous effect on stopping cancer progression in the majority of chronic myeloid leukemia patients. BCR-Abl is ...
... which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine ... First, there exists a highly positive correlation (Spearman's rho = 0.81; P < 3.5 × 10−8) between the risk of developing cancer ... and miR-29b in chronic lymphocytic leukemia". Blood. 119 (5): 1162-72. doi:10.1182/blood-2011-05-351510. PMC 3277352. PMID ... Thus, the usual consequence of H. pylori infection is chronic asymptomatic gastritis. Because of the usual lack of symptoms, ...
Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl ... In the gut, however, a mass staining positive for CD117 is likely to be a GIST, arising from ICC cells. The c-KIT molecule ... of all GISTs are CD117-positive (other possible markers include CD34, DOG-1, desmin, and vimentin). Other cells that show CD117 ...
In both of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML), MSI2 regulates hematopoietic stem cell ... It has been found that MSI2 participates together with BCR-ABL gene to stimulate the progress to the aggressive phase. The ... positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22". Haematologica. 93 (12): 1903-7. ... Chronic myelogenous leukemia (CML) progresses from the initial phase, where differentiated myeloid cells are accumulated, to ...
In chronic myelogenous leukemia (CML), GAB2 interacts with the Bcr-Abl complex and is instrumental in maintaining the oncogenic ... By binding to the p85 subunit of PI3K, and continuing this signaling pathway GAB provides positive feedback for the creation of ... The Grb2/GAB2 complex is recruited to phosphorylated Y177 of the Bcr-Abl complex leading to Bcr-Abl-mediated transformation and ... "Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2". ...
... "e19a2-positive chronic myeloid leukaemia with BCR exon e16-deleted transcripts". Leukemia. 16 (8): 1562-3. doi:10.1038/sj.leu. ... The BCR-ABL oncoprotein oligomerisation domain found at the N-terminus of BCR is essential for the oncogenicity of the BCR-ABL ... which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is ... Kolibaba KS, Bhat A, Heaney C, Oda T, Druker BJ (March 1999). "CRKL binding to BCR-ABL and BCR-ABL transformation". Leuk. ...
... in complex with an Abl kinase domain (blue). Nilotinib is used to treat chronic myelogenous leukemia (CML), a hematological ... "Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells". Nat Med. 2 (5): 561-6. ... For example, they have substantially improved outcomes in chronic myelogenous leukemia. They are also called tyrphostins, the ... Based on this work imatinib was developed against chronic myelogenous leukemia (CML)[6] and later gefitinib and erlotinib ...
As chemotherapy affects cell division, tumors with high growth rates (such as acute myelogenous leukemia and the aggressive ... a genetic lesion found commonly in chronic myelomonocytic leukemia. This fusion protein has enzyme activity that can be ... The FOLFOX study also demonstrated an improvement in treatment outcomes.[22] Positive response increased from 46% in the BSA- ... bcr-abl *Imatinib. *Dasatinib. *Nilotinib. *Ponatinib. *Radotinib. *Src (Bosutinib. *Dasatinib). *Janus kinase *Lestaurtinib ...
Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML).[4] ... Ehrenreich, Barbara (2009). Bright-sided: How the Relentless Promotion of Positive Thinking Has Undermined America. Henry Holt ... which occurs in chronic myelogenous leukemia and results in production of the BCR-abl fusion protein, an oncogenic tyrosine ... and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in ...
... has been used as an engineered "control switch" in chronic myelogenous leukemia models in mice. Engineers were ... "Rapid generation of a tetracycline-inducible BCR-ABL defective retrovirus using a single autoregulatory retroviral cassette".. ... both Gram-positive and Gram-negative, with a few exceptions, such as Pseudomonas aeruginosa and Proteus spp., which display ... able to develop a retrovirus that induced a particular type of leukemia in mice, and could then "switch" the cancer on and off ...
In the case of Gleevec (Imatinib), which targets the BCR-ABL fusion gene in chronic myeloid leukemia, resistance often develops ... including the Philadelphia chromosome in chronic myelogenous leukemia[14] and translocations in acute myeloblastic leukemia.[15 ... Selective estrogen receptor modulators (SERMs) are a commonly used adjuvant therapy in estrogen-receptor positive (ERα+) breast ... a study of chronic myelogenous leukemia". Am. J. Hum. Genet. 18 (5): 485-503. PMC 1706184 . PMID 5224748.. ...
... in chronic myelogenous leukemia progenitor cells". Blood. 93 (8): 2707-20. doi:10.1182/blood.V93.8.2707. PMID 10194451. Leitges ... and Bcr-Abl". Blood. 89 (8): 2745-56. doi:10.1182/blood.V89.8.2745. PMID 9108392. Liu L, Damen JE, Ware MD, Krystal G (April ... Eissmann P, Beauchamp L, Wooters J, Tilton JC, Long EO, Watzl C (June 2005). "Molecular basis for positive and negative ... "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells ...
Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, ... BCR-ABL1-positive Chronic neutrophilic leukaemia Polycythaemia vera Primary myelofibrosis Essential thrombocythaemia Chronic ... BCR-ABL 1―like B-lymphoblastic leukaemia/lymphoma with iAMP21 T-lymphoblastic leukaemia/lymphoma Early T-cell precursor ... leg type EBV-positive DLBCL, NOS EBV-positive mucocutaneous ulcer DLBCL associated with chronic inflammation Fibrin-associated ...
... acute lymphocytic leukemia (ALL), Philadelphia chromosome negative chronic myelogenous leukemia (Ph(-)CML), myelodysplastic ... "Nucleotide sequence analysis of human abl and bcr-abl cDNAs". Oncogene. 4 (12): 1477-81. PMID 2687768. Buijs A, Sherr S, van ... "Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3". Blood ... chronic myelomonocytic leukemia, acute myelocytic leukemia, B cell acute lymphoblastic leukemia, mixed phenotype acute leukemia ...
... a small molecule BCR-ABL and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia, which had $ ... "FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative ... On September 4, 2012, the FDA approved bosutinib (Bosulif) for chronic myelogenous leukemia (CML), a rare type of leukemia and ... Yukhananov, Anna (September 4, 2012). "FDA approves Pfizer leukemia drug". Reuters. "Drug Approval Package". Food and Drug ...
In in vitro studies of chronic myelogenous leukemia (CML), siRNA was used to cleave the fusion protein, BCR-ABL, which prevents ... and positive-strand RNA viruses". Virology. 313 (2): 514-24. doi:10.1016/s0042-6822(03)00341-6. PMID 12954218. Fan Q, Wei C, ... These experiments have suggested that siRNA may be used to combat other respiratory diseases, such as chronic obstructive ... In addition to mucus hypersecretion, chronic inflammation and damaged lung tissue are characteristic of COPD and asthma. The ...
... affinity for the oncofusion protein BCR-Abl which is a strong driver of tumorigenesis in chronic myelogenous leukemia. Although ... "Phase II study of AEZS-108 (AN-152), a targeted cytotoxic LHRH analog, in patients with LHRH receptor-positive platinum ... Imatinib (Gleevec, also known as STI-571) is approved for chronic myelogenous leukemia, gastrointestinal stromal tumor and some ... Gleevec is most effective targeting BCR-Abl. Other examples of molecular targeted therapeutics targeting mutated oncogenes, ...
Search of: Recruiting, Not yet recruiting, Available Studies , Leukemia, Myelogenous, Chronic, BCR-ABL Positive - Modify ...
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*Leukemia, Myelogenous, Chronic, BCR-ABL Positive ... Chronic, BCR-ABL Positive" by people in this website by year, and whether "Leukemia, Myelogenous, Chronic, BCR-ABL Positive" ... "Leukemia, Myelogenous, Chronic, BCR-ABL Positive" is a descriptor in the National Library of Medicines controlled vocabulary ... Below are the most recent publications written about "Leukemia, Myelogenous, Chronic, BCR-ABL Positive" by people in Profiles. ...
Philadelphia chromosome positive OR. *BCR/ABL rearrangement. *No blast crisis or post blast crisis ... Histologically confirmed chronic or accelerated phase chronic myelogenous leukemia. * ... Chemotherapy, Filgrastim and Peripheral Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia. The safety and ... Autologous Transplantation for Chronic Myelogenous Leukemia Using Retrovirally Marked Peripheral Blood Progenitor Cells ...
... we tested the hypothesis that cytokine-independent growth of leukemia cells results from aberrant activation of cytokine ... Using chronic myelogenous leukemia (CML) as a model, ... Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics * ... Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism * Leukemia, Myelogenous, Chronic, BCR-ABL Positive / ... Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia Oncogene. 1996 Jul 18;13(2):247-54. ...
Chronic myeloid leukemia (CML) is a cancer of the white blood cells. It usually affects older adults. Learn about symptoms, ... Chronic, BCR-ABL Positive (National Institutes of Health) * ClinicalTrials.gov: Leukemia, Myeloid, Chronic, Atypical, BCR-ABL ... Chronic Myeloid Leukemia Also called: Chronic granulocytic leukemia, Chronic myelogenous leukemia, CML ... What is chronic myeloid leukemia (CML)? Chronic myeloid leukemia (CML) is a type of chronic leukemia. "Chronic" means that the ...
Leukemia. Leukemia, Myeloid. Leukemia, Myelogenous, Chronic, BCR-ABL Positive. Leukemia, Myeloid, Chronic-Phase. Neoplasms by ... chronic phase chronic myelogenous leukemia. chronic myelogenous leukemia, BCR-ABL1 positive. relapsing chronic myelogenous ... rate in patients with imatinib mesylate-resistant Philadelphia chromosome-positive chronic phase chronic myelogenous leukemia ... Diagnosis of chronic phase chronic myelogenous leukemia (CML), meeting all of the following criteria:. *Less than 15% blasts in ...
... triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia ... Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation ... Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation ... Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation ...
To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous ... Leukemia, Myeloid. *Leukemia, Myelogenous, Chronic, BCR-ABL Positive. .map{width:100%;height:300px;margin-bottom:15px}. Name. ... A Phase II, Multicenter Study of Decitabine (5-Aza-2Deoxycytidine) in Chronic Myelogenous Leukemia Accelerated Phase ... A Phase II, Multicenter Study of Decitabine (5-Aza-2Deoxycytidine) in Chronic Myelogenous Leukemia Accelerated Phase ...
High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease ... Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics* * Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism ... Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1 ... hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera ...
Leukemia, Myelogenous, Chronic, BCR-ABL Positive. D015464. EFO:0000339. chronic myelogenous leukemia. 3. ClinicalTrials. ... Tyrosine-protein kinase ABL inhibitor Tyrosine-protein kinase ABL DailyMed Indications MESH Heading. MESH ID. EFO ID. EFO Term ... Leukemia, Lymphoid. D007945. EFO:0004289. lymphoid leukemia. 3. ClinicalTrials. Peritoneal Neoplasms. D010534. EFO:1001100. ... Leukemia, Myeloid, Acute. D015470. EFO:0000222. acute myeloid leukemia. 2. ClinicalTrials. ClinicalTrials. ...
Leukemia, Myelogenous, Chronic, BCR-ABL Positive. D015464. EFO:0000339. chronic myelogenous leukemia. 2. ClinicalTrials. ... chronic lymphocytic leukemia. 4. ClinicalTrials. Leukemia, Mast-Cell. D007946. EFO:0007359. mast-cell leukemia. 2. ... Leukemia, Hairy Cell. D007943. EFO:1000956. hairy cell leukemia. 2. ClinicalTrials. Lymphoma, Large-Cell, Anaplastic. D017728. ... Leukemia. D007938. EFO:0000565. leukemia. 3. ClinicalTrials. Liver Cirrhosis, Biliary. D008105. EFO:1001486. primary biliary ...
... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ...
... abl transcript and clinical details derived from 64 chronic myelogenous leukemi ... We report here the results of polymerase chain reaction (PCR) for bcr- ... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ... bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia ...
Philadelphia chromosome positive OR. - BCR/ABL rearrangement. - Ineligible or refused to participate in ongoing allogeneic ... Histologically confirmed chronic or accelerated phase chronic myelogenous leukemia. (CML). - ... accelerated phase chronic myelogenous leukemia when treated with cyclophosphamide and. filgrastim (G-CSF) followed by ... Autologous Marrow Transplantation for Chronic Myelogenous Leukemia Using Stem Cells Obtained After In Vivo Cyclophosphamide/G- ...
Leukemia, Lymphocytic, Chronic, B-Cell. Leukemia, Myelogenous, Chronic, BCR-ABL Positive. Leukemia, T-Cell. Leukemia-Lymphoma, ... Chronic Lymphocytic Leukemia Leukemia, T-cell, Chronic Adult T-cell Leukemia/lymphoma Chronic Myelomonocytic Leukemia Juvenile ... Leukemias Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Adult T Cell Leukemia (ATL) Chronic Myeloid Leukemia ( ... adult T cell leukemia (ATL). *chronic myeloid leukemia in blast crisis (CML-BP) having failed Bcr-Abl specific kinase ...
Lineage switch is a very rare event in blastic crisis of chronic myelogenous leukemia (CML-BC). To our knowledge, only three ... Leukemia, B-Cell / pathology*. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*. Male. ... Lineage switch is a very rare event in blastic crisis of chronic myelogenous leukemia (CML-BC). To our knowledge, only three ... Previous Document: Mean cell volume can be an early predictor for the cytogenetic response of chronic myeloid leukemia .... ...
... triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia ... cells were found in chronic myelogenous leukemia patients with continuous BCR-ABL gene expression but undetectable BCR-ABL ... Imatinib Mesylate Resistance Through BCR-ABL Independence in Chronic Myelogenous Leukemia. Nicholas J. Donato, Ji Y. Wu, ... Imatinib Mesylate Resistance Through BCR-ABL Independence in Chronic Myelogenous Leukemia. Nicholas J. Donato, Ji Y. Wu, ...
... chronic myelogenous leukemia (CML) have been associated with an inferior outcome in reported series of largely chemotherapy- ... Secondary cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive (Ph+) ... Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*, genetics, mortality. Male. Middle Aged. Prognosis. Survival ... Secondary cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) ...
Imatinib is used in the treatment of gastrointestinal stromal tumor; chronic myelogenous leukemia; acute lymphoblastic leukemia ... BCR-ABL tyrosine kinase inhibitors. Pregnancy Category:. D - Positive evidence of risk. CSA Schedule:. Not a controlled drug. ... and belongs to the drug class BCR-ABL tyrosine kinase inhibitors. There is positive evidence of human fetal risk during ...
Prognostic factors for chronic myelogenous leukemia include your age and the phase of the cancer. Learn about prognosis and ... This translocation creates the BCR-ABL fusion gene, which leads to the development of CML. ... When the Ph chromosome is present, CML is described as Ph-positive, or Ph+, CML. When the Ph chromosome isnt present, it is ... Prognosis and survival for chronic myelogenous leukemia. People with chronic myelogenous leukemia (CML) may have questions ...
Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive ... chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with ... Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia ... Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia ...
Leukemia, Myelogenous, Chronic, Bcr-abl Positive. Clonal hematopoetic disorder caused by an acquired genetic defect in ... The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, ... Protein Biomarker Discovery and Validation in Chronic Obstructive Pulmonary Disease (COPD) And Asthma ... to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS. ...
... chromosome positive chronic myelogenous leukemia (CML), and effect not mediated by DNA methylation. Koyu Hoshino, Hui Yang, ... CML is molecularly defined by the presence of the BCR-ABL oncoprotein. This protein has unregulated protein tyrosine kinase ... chromosome positive chronic myelogenous leukemia (CML), and effect not mediated by DNA methylation ... chromosome positive chronic myelogenous leukemia (CML), and effect not mediated by DNA methylation ...
A metaphase cell positive for the bcr/abl rearrangement (associated with chronic myelogenous leukemia) using FISH. The ... chronic myelogenous leukemia, acute lymphoblastic leukemia, Cri-du-chat, Velocardiofacial syndrome, and Down syndrome. FISH on ... An example is the detection of BCR/ABL translocations, where the secondary color indicates disease. This variation is often ... such as translocations and inversions which are hallmark aberrations seen in many types of leukemia and lymphoma. ...
For instance the old descriptor LEUKEMIA, MYELOID, CHRONIC is now called LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE. The ... old descriptor LEUKEMIA, MYELOID, PHILADELPHIA-NEGATIVE is now LEUKEMIA, MYELOID, CHRONIC, ATYPICAL, BCR-ABL NEGATIVE. ... Leukemia - Lymphoma Changes. The official nomenclature in this field has gone through many changes over the years and the MeSH ... Many of the leukemia terms have undergone name changes as immunophenotypic and molecular biological techniques have made ...
Hematology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute * Appt 203.200.4363 ...
Leukemia, Myelogenous, Chronic, Bcr-abl Positive. *Lymphomatoid Granulomatosis. *Macular Degeneration. *Malignant Carcinoid ... Interferon alfa-2b is a prescription medication used to treat chronic hepatitis B, chronic hepatitis C, certain type of genital ... chronic (lasting a long time) hepatitis C infection in people 3 years and older with stable liver problems (along with another ... chronic (lasting a long time) hepatitis B infection in people 1 year and older with stable liver problems ...
Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES. ... Acute Myeloid Leukemia: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. ... Acute Myeloid Leukemia (Acute Myelogenous Leukemia) 5. BCR-ABL Positive Chronic Myelogenous Leukemia (Chronic Myelogenous ... Acute Myelogenous Leukemia; Acute Myeloblastic Leukemia; Myelogenous Leukemia, Acute; Acute Myelocytic Leukemia; Acute ...
To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic ... myeloid leukemia cells. Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-su ... Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*, pathology. Membrane Potential, Mitochondrial / drug effects. ... and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. ...
  • Although small-molecule inhibitors that inhibit protein tyrosine kinases are showing promise in the clinic, a growing problem for the treatment of acute leukemia patients is the development of resistance resulting from acquired point mutations in the targeted kinases ( 13 , 14 ). (aacrjournals.org)
  • Nilotinib hydrochloride monohydrate blocks BCR-ABL and other proteins, which may help keep cancer cells from growing. (cancer.gov)
  • Studies suggest that these proteins may be a viable target in leukemia because they have been found to be variably expressed in acute leukemias and are associated with chemosensitivity, chemoresistance, disease progression, remission, and patient survival. (aacrjournals.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)
  • Heat shock protein 90 (Hsp90) is a highly conserved, constitutively expressed molecular chaperone that facilitates folding of client proteins such as BCR-ABL, and affects the stability of these proteins. (bloodjournal.org)
  • Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. (sciencemag.org)
  • In some cases the distinctions between leukemias and lymphomas are now considered artificial, and so the nomenclature contains new descriptors such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA. (nih.gov)
  • STAT5 was also activated in primary mouse bone marrow cells acutely transformed by the CML-specific BCR-ABL oncogene, but not by the serine kinase oncogene v-MOS. (nih.gov)
  • This translocation fuses the breakpoint cluster region ( Bcr ) and the Abl genes and creates the BCR-ABL oncogene ( 4 ). (pnas.org)
  • The causative agent for 95% of all CML cases, Bcr-Abl, is derived from the fusion of the breakpoint cluster region (Bcr) gene on chromosome 22 and the Abelson leukemia oncogene (Abl) on chromosome 9. (pubmedcentralcanada.ca)
  • Some mutations create a more potent Bcr-Abl oncogene and accelerate disease progression[ 9 ]. (pubmedcentralcanada.ca)
  • In the cytoplasm Bcr-Abl acts as an oncogene by interacting with multiple signal transduction pathways that transmit anti-apoptotic and mitogenic signals[ 14 ]. (pubmedcentralcanada.ca)
  • Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells. (uptodate.com)
  • Alternative chimeric oncogenes are formed by splicing different sets of BCR gene exons on chromosome 22 across the translocation breakpoint to a common set of ABL oncogene sequences on chromosome 9. (uptodate.com)
  • Changes in mitogenic potency may help to explain the more acute leukemic presentation usually associated with expression of the P185 BCR-ABL oncogene. (uptodate.com)
  • Recent studies provide evidence that implicate c-Abl as a mediator for fibrotic responses induced by transforming growth factor-β (TGF-β), but the precise mechanisms underlying this novel oncogene function are unknown. (elsevier.com)
  • 1 The resulting chimeric BCR-ABL oncogene encodes a constitutively activated, oncogenic tyrosine kinase that induces chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL). (bloodjournal.org)
  • 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. (sciencemag.org)
  • gastrointestinal stromal tumor and belongs to the drug class BCR-ABL tyrosine kinase inhibitors . (drugs.com)
  • Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance to BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous leukemia (CML). (jci.org)
  • Different inhibitors have been designed to target different kinases: inhibition of BCR/ABl constitutes the basis of the functioning of drugs like imatinib inhibition of FLT3 is carried out by drugs like lestaurtinib inhibition of JAK2 is carried out by the drug CYT387, which was successful in preclinical trials and is currently undergoing clinical trials. (wikipedia.org)
  • Homozygosity for killer immunoglobin-like receptor haplotype A predicts complete molecular response totreatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients," Experimental Hematology , vol. 41, no. 5, pp. 424-431, 2013. (hindawi.com)
  • Member has Philadelphia chromosome-positive ALL refractory to tyrosine kinase inhibitors (TKIs). (aetna.com)
  • 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)
  • Farnesyltransferase inhibitors, such as SCH66336, and the proteasome inhibitor Bortezomib have been shown to have growth inhibitory effects on certain imatinib-resistant leukemias ( 12 ). (pnas.org)
  • The ABL-kinase inhibitors (AKIs) Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. (uni-frankfurt.de)
  • Conclusions: Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors. (uni-frankfurt.de)
  • Targeted inhibition of BCR/ABL by small molecule inhibitors reverses the transformation potential of BCR/ABL. (uni-frankfurt.de)
  • Many other tyrosine kinase inhibitors (TKIs) are being studied and developed, with a few already approved nonetheless, Bcr-Abl also has the potential to develop resistance to these molecules. (pubmedcentralcanada.ca)
  • 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)
  • The discovery of tyrosine kinase inhibitors (TKIs) revolutionized therapy for CML, such that durable response, increased overall survival, and increased progression-free survival of patients in chronic phase CML is now possible. (dovepress.com)
  • A particularly challenging example is found in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) where all available kinase inhibitors in clinic are ineffective against the BCR-ABL mutant, T315I. (bloodjournal.org)
  • Rather than inhibiting kinase activity, elimination of mutant kinases provides a new therapeutic strategy for treating BCR-ABL-induced leukemia as well as other cancers resistant to treatment with tyrosine kinase inhibitors. (bloodjournal.org)
  • Three newly developed BCR-ABL kinase inhibitors-dasatinib, 12 AP23464, 13 and AMN107 14 -inhibit most of imatinib-resistant BCR-ABL mutants at biochemical and cellular levels, but are ineffective against the BCR-ABL-T315I mutant. (bloodjournal.org)
  • Many targeted therapies for the treatment of non-small cell lung cancer (NSCLC) and the other malignancies are associated with ILD, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), anaplastic lymphoma kinase (ALK) inhibitors, angiogenesis inhibitors, Bcr-Abl tyrosine kinase inhibitors, human epidermal growth factor receptor 2 (HER2) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, various monoclonal antibodies, etc [ 1 , 4 ]. (omicsonline.org)
  • With the introduction of tyrosine kinase inhibitors (TKIs), prognosis of chronic myelogenous leukemia (CML) has improved dramatically. (springer.com)
  • Resistance to or intolerance of imatinib in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) has encouraged the development of more potent Bcr-Abl inhibitors. (aacrjournals.org)
  • The landscape of BCR-ABL mutations in patients with Philadelphia chromosome-positive leukaemias in the era of second-generation tyrosine kinase inhibitors. (harvard.edu)
  • Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia. (harvard.edu)
  • Downregulation of miR-217 correlates with resistance of Ph(+) leukemia cells to ABL tyrosine kinase inhibitors. (nih.gov)
  • The onset of ABL point mutations is the most frequent identified mechanism responsible for resistance. (haematologica.org)
  • BCR-ABL T315I mutations have been identified in the 5 different laboratories and clinical data were retrospectively collected according to each centre ethical guidelines. (haematologica.org)
  • IM resistance has been associated with kinase mutations or increased BCR-ABL expression. (aacrjournals.org)
  • 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)
  • Of growing concern, however, is the development of drug resistance resulting from the emergence of point mutations in targeted tyrosine kinases used for treatment of acute leukemia patients. (aacrjournals.org)
  • This is mostly due to mutations in the Bcr-Abl kinase domain that render it unable to bind to Gleevec[ 6 - 8 ]. (pubmedcentralcanada.ca)
  • 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 BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosome-positive (Ph-positive) leukemias, but relapse occurs, mainly as a result of the outgrowth of leukemic subclones with imatinib-resistant BCR-ABL mutations. (nih.gov)
  • We evaluated dasatinib, a BCR-ABL inhibitor that targets most imatinib-resistant BCR-ABL mutations, in patients with chronic myelogenous leukemia (CML) or Ph-positive acute lymphoblastic leukemia (ALL). (nih.gov)
  • 17 - 21 When BCR-ABL contains resistance-conferring mutations, it becomes even more dependent on Hsp90 in vitro. (bloodjournal.org)
  • Determine the 12-week major cytogenetic response (MCyR) rate in patients with imatinib mesylate-resistant Philadelphia chromosome-positive chronic phase chronic myelogenous leukemia treated with BMS-354825 vs imatinib mesylate. (clinicaltrials.gov)
  • 6 , 7 In this multicentric retrospective study, we analysed 27 BCR-ABL T315I mutated CML patients exhibiting either clinical, cytological, cytogenetic resistance or molecular progression. (haematologica.org)
  • Resistance was defined according to the ELN guidelines 3 and if any hematological, cytogenetic or molecular progression ( i.e. increasing BCR-ABL/ABL ratio ≥ 2 logs) of CML in a previously IM-responsive patient was observed. (haematologica.org)
  • Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study. (biomedsearch.com)
  • Secondary cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) have been associated with an inferior outcome in reported series of largely chemotherapy-treated patients. (biomedsearch.com)
  • A report of early cytogenetic response to imatinib in two patients with chronic myeloid leukemia at accelerated phase and carrying the e19a2 BCR-ABL transcript," Cancer Genetics and Cytogenetics , vol. 176, no. 2, pp. 166-168, 2007. (hindawi.com)
  • Neben K, Giesecke C, Schweizer S, Ho AD, Krämer A: Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile. (uni-heidelberg.de)
  • Based on the presence of t(9;22)(q34;q11) on cytogenetic study and a positive result for Major bcr/abl fusion gene, a diagnosis of CML-CP was established. (unboundmedicine.com)
  • The Philadelphia chromosome (Ph) ( 1 ), arising from a balanced translocation involving chromosomes 9 and 22 ( 2 ), is the founding genetic lesion and cytogenetic hallmark of chronic myelogenous leukemia (CML) and of a subset of Ph + acute lymphoblastic leukemias (ALLs). (pnas.org)
  • Dasatinib induces hematologic and cytogenetic responses in patients with CML or Ph-positive ALL who cannot tolerate or are resistant to imatinib. (nih.gov)
  • The BCR-ABL TKI, imatinib mesylate, induces a complete hematologic and cytogenetic response in the majority of chronic-phase CML patients, 2 but is unable to completely eradicate BCR-ABL-expressing leukemic cells, 3 , 4 suggesting that leukemia stem cells are not eliminated. (bloodjournal.org)
  • Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months ( BCR-ABL1 transcript level ≤10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months). (jnccn.org)
  • Research data pertaining to possible cytogenetic mechanisms leading to production of p210 bcr-abl in the absence of the Ph chromosome are reviewed. (annals.org)
  • We analyzed 27 CML patients treated with imatinib (IM) who developed a BCR-ABL T315I mutation. (haematologica.org)
  • Twenty-seven CML patients [17 males, 10 females, median age at diagnosis 52 (25-70) months] harboring a BCR-ABL T315I mutation were recorded. (haematologica.org)
  • A T315I mutation in e19a2 BCR/ABL1 chronic myeloid leukemia responding to dasatinib," Leukemia Research , vol. 34, no. 9, pp. e240-e242, 2010. (hindawi.com)
  • 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)
  • Given the fact that all AKIs fail to inhibit BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. (uni-frankfurt.de)
  • Methods: The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC) from Ph + ALL-patients. (uni-frankfurt.de)
  • Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner. (uni-frankfurt.de)
  • Responses occurred among all BCR-ABL genotypes, with the exception of the T315I mutation, which confers resistance to both dasatinib and imatinib in vitro. (nih.gov)
  • Treatment with IPI-504 resulted in BCR-ABL protein degradation, decreased numbers of leukemia stem cells, and prolonged survival of leukemic mice bearing the T315I mutation. (bloodjournal.org)
  • Hsp90 inhibition more potently suppressed T315I-expressing leukemia clones relative to the wild-type (WT) clones in mice. (bloodjournal.org)
  • 20 We therefore evaluated the therapeutic effect of Hsp90 inhibition by using a novel water-soluble inhibitor, IPI-504, 22 in drug-resistant animal models of leukemia induced by BCR-ABL-WT and T315I. (bloodjournal.org)
  • To generate the BCR-ABL-expressing 32D or BaF/3 line, the cells were transduced with the BCR-ABL-WT- or BCR-ABL-T315I-IRES-GFP-MSCV retrovirus, and the BCR-ABL-expressing cells were selected by GFP sorting by fluorescence-activated cell sorter (FACS). (bloodjournal.org)
  • PURPOSE: This randomized phase II trial is studying BMS-354825 to see how well it works compared to imatinib mesylate in treating patients with chronic phase chronic myelogenous leukemia that did not respond to previous imatinib mesylate. (clinicaltrials.gov)
  • Assess the clinical outcomes, survival, and morbidity of patients with chronic or accelerated phase chronic myelogenous leukemia when treated with cyclophosphamide and filgrastim (G-CSF) followed by autologous peripheral blood stem cell transplantation. (knowcancer.com)
  • Whereas FIP1L1-PDGFRα alone induced acute T-cell leukemia or myeloproliferative neoplasms in mouse bone marrow transplantation models, mice transplanted with bone marrow cells expressing both Hes1 and FIP1L1-PDGFRα developed acute leukemia characterized by an expansion of myeloid blasts and leukemic cells without eosinophilic granules. (nih.gov)
  • 90% of CML cases, it has been possible to synthesize small molecules that inhibit BCR-ABL kinase activity in leukemic cells without adversely affecting the normal cell population. (pnas.org)
  • We have previously shown that dendritic cells (DC) may be generated from leukemic cells of chronic myelogenous leukemia and acute myelogenous leukemia patients and that these DC may be used to stimulate autologous anti-leukemic cytotoxic cells. (elsevier.com)
  • The constitutive activation of the ABL-kinase in BCR/ABL cells induces the leukemic phenotype. (uni-frankfurt.de)
  • To determine whether GAP expression is required for the growth of human normal and leukemic hematopoietic cells, we used GAP antisense oligodeoxynucleotides to inhibit it and analyzed the effects of this inhibition on the colony-forming ability of nonadherent, T lymphocyte-depleted mononuclear cells and of highly purified progenitors (CD34+ MNC) obtained from the bone marrow and peripheral blood of healthy volunteers or chronic myeloid leukemia (CML, bcr-abl-positive) patients. (rupress.org)
  • These data indicate that p120 GAP is involved in human normal and leukemic hemopoiesis and strongly suggest that GAP is not only a p21ras inhibitor (signal terminator), but also a positive signal transducer. (rupress.org)
  • JAK2 mutation: positive in about 50% of patients, but not specific for ET and may be present in other myeloproliferative disorders. (clinicaladvisor.com)
  • If ET is suspected, get JAK2 mutation which helps exclude reactive causes if it is positive. (clinicaladvisor.com)
  • 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)
  • 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)
  • 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)
  • This results in an 8.7-kilobase mRNA that encodes the P210 BCR-ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7.0-kilobase mRNA that produces the P185 BCR-ABL gene product found in most Philadelphia chromosome-positive patients with acute lymphocytic leukemia. (uptodate.com)
  • Marked leukocytosis with p210 BCR-ABL1 mRNA positivity and Philadelphia chromosome detected by bone marrow biopsy confirmed the diagnosis of CML. (springer.com)
  • en] This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). (ac.be)
  • 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)
  • 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)
  • They used Gleevec to stimulate Bcr-Abl to go to the nucleus (by unknown mechanism), followed by nuclear entrapment by leptomycin B (LMB), a general inhibitor of nuclear export. (pubmedcentralcanada.ca)
  • 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)
  • These results provide a rationale for use of an Hsp90 inhibitor as a first-line treatment in CML by inhibiting leukemia stem cells and preventing the emergence of imatinib-resistant clones in patients. (bloodjournal.org)
  • The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. (jnccn.org)
  • AMN107 is a novel, orally bioavailable ATP-competitive inhibitor of Bcr-Abl. (aacrjournals.org)
  • Imatinib, a competitive inhibitor of the BCR/ABL tyrosine kinase, is the common treatment of CML. (scirp.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)
  • The constitutively activated BCR/ABL-kinase 'escapes' the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. (uni-frankfurt.de)
  • Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. (uni-frankfurt.de)
  • Collectively, these results position Egr-1 downstream of c-Abl in the fibrotic response, delineate a novel Egr-1-dependent intracellular signaling mechanism that underlies the involvement of c-Abl in certain TGF-β responses, and identify Egr-1 as a target of inhibition by imatinib. (elsevier.com)
  • A metaphase cell positive for the bcr/abl rearrangement (associated with chronic myelogenous leukemia ) using FISH. (wikipedia.org)
  • BCR-ABL gene rearrangement to evaluate for CML. (clinicaladvisor.com)
  • We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region ( bcr ) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. (annals.org)
  • Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. (annals.org)
  • Thus, our data suggests that for chronic myelomonocytic leukemia the cytokine combination of GMCSF. (elsevier.com)
  • Prognostic Factors and Scoring Systems in Chronic Myelomonocytic Leukemia: a Retrospective Analysis of 213 Patients Blood. (jove.com)
  • Pubmed ID: 11806985 Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. (jove.com)
  • 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. (umassmed.edu)
  • Clinically, CML is divided into three different phases: initial phase known as chronic (CP), that is followed by an accelerated phase (AP), and a final fatal phase known as blastic (BP). (aacrjournals.org)
  • A complete hematologic response was achieved in 37 of 40 patients with chronic-phase CML, and major hematologic responses were seen in 31 of 44 patients with accelerated-phase CML, CML with blast crisis, or Ph-positive ALL. (nih.gov)
  • Responses were maintained in 95 percent of patients with chronic-phase disease and in 82 percent of patients with accelerated-phase disease, with a median follow-up more than 12 months and 5 months, respectively. (nih.gov)
  • BOSULIF was first approved in September 2012 in the U.S. for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy. (businesswire.com)
  • In the U.S., BOSULIF (bosutinib) is now indicated for the treatment of patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) and for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy (first approved in September 2012). (businesswire.com)
  • Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. (aetna.com)
  • Although Gleevec is currently the "gold standard" drug of choice for Bcr-Abl-positive CML[ 3 - 5 ], resistance to treatment with Gleevec occurs. (pubmedcentralcanada.ca)
  • Other mechanisms for resistance include Bcr-Abl amplification or overexpression, clonal evolution, a decrease in Gleevec bioavailability or cell exposure, and upregulation of drug efflux pumps[ 6 , 10 ]. (pubmedcentralcanada.ca)
  • Kuroda, J., Kimura, S., Andreeff, M., et al (2007) ABT-737 is a useful component of combinatory chemo-therapies for chronic myeloid leukaemias with diverse drug-resistance mechanisms. (scirp.org)
  • Dulucq, S., Bouchet, S., Turcq, B., et al (2008) Mul-tidrug resistance gene (MDR1) polymorphisms are asso-ciated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia. (scirp.org)
  • Kikuchi, S., Nagai, T., Kunitam, M., et al (2007) Active FKHRL1 overcomes imatinib resistance in chronic mye-logenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand. (scirp.org)
  • Baran, Y., Salas, A., Senkal, C., et al (2007) Alterations of ceramide/sphingosine 1-phosphate rheostat involved in the regulation of resistance to imatinib-induced apop-tosis in K562 human chronic myeloid leukemia cells. (scirp.org)
  • Apoptotic effects of resveratrol, a grape polyphenol, on imatinib-sensitive and resistant K562 chronic myeloid leukemia cells. (biomedsearch.com)
  • AIM: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. (biomedsearch.com)
  • On the other hand, nuclear entrapment of endogenous Bcr-Abl (in K562 human leukemia cells) causes apoptosis. (pubmedcentralcanada.ca)
  • The goal of this study was to determine whether plasmid expressed Bcr-Abl could cause apoptosis of K562 cells when specifically directed to the nucleus via strong nuclear localization signals (NLSs). (pubmedcentralcanada.ca)
  • When transfected into K562 cells, only 4NLS-Bcr-Abl translocated to the nucleus. (pubmedcentralcanada.ca)
  • Vigneri and Wang have previously shown that nuclear entrapment of Bcr-Abl in K562 cells results in apoptosis, and requires an active tyrosine kinase domain to do so[ 2 ]. (pubmedcentralcanada.ca)
  • As controls, we studied 6 bone marrows from healthy volunteers, 3 cases of acute lymphocytic leukemia (ALL) and 11 leukemia derived cell lines. (aacrjournals.org)
  • Seggewiss R, Ho AD, Krämer A: Remarkable response to rituximab in a patient with atypical CD20++ B-cell chronic lymphocytic leukemia of the bone marrow leading to severe pancytopenia. (uni-heidelberg.de)
  • The Philadelphia chromosome (t9:22;q34:q11) is found in more than 90% of patients with chronic myelogenous leukemia, in 10 to 20% of patients with acute lymphocytic leukemia, and in 1 to 2% of patients with acute myelogenous leukemia. (uptodate.com)
  • 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). (sciencemag.org)
  • In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. (sciencemag.org)
  • Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph1-positive ALL SUP-B15 cell line, and S1 nuclease protection analysis confirmed the presence of BCR-ABL chimeric transcripts in Ph1-positive ALL cells. (sciencemag.org)
  • We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). (elsevier.com)
  • A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. (elsevier.com)
  • Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. (elsevier.com)
  • To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. (elsevier.com)
  • A BCR-ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. (jnccn.org)
  • Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. (jnccn.org)
  • Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. (jnccn.org)
  • The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. (jnccn.org)
  • Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. (uni-frankfurt.de)
  • The resulting Bcr-Abl fusion protein acts as an oncoprotein, and the constitutive activation of tyrosine kinase activity of Abl leads to cell proliferation. (pubmedcentralcanada.ca)
  • After washout of Gleevec, Bcr-Abl's tyrosine kinase activity is re-activated, and the cells undergo spontaneous apoptosis. (pubmedcentralcanada.ca)
  • BCR/ABL has constitutively tyrosine kinase activity resulting in leukemogenesis. (scirp.org)
  • Krämer A, Hager H-D, Fruehauf S, Hochhaus A, Bartram CR, Ho AD: Novel constitutional t(2;12)(q21;q22) in a patient with t(9;22)-negative chronic myelocytic leukemia. (uni-heidelberg.de)
  • 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). (harvard.edu)
  • CML is molecularly defined by the presence of the BCR-ABL oncoprotein. (aacrjournals.org)
  • 2 Imatinib mesylate, the first TKI to specifically target the BCR-ABL1 oncoprotein, 3 was introduced into trials in 1998. (hematology.org)
  • Prognostic discrimination in "good-risk" chronic granulocytic leukemia. (springer.com)
  • Results using BCR-ABL mutants which specifically uncouple connections to known signal transduction pathways show that STAT5 activation is kinase dependent and correlates directly with ability to confer cytokine independent growth in hematopoietic cells. (nih.gov)
  • The immunogenicity of the CML-specific tumour antigen, BCR-ABL, has been the subject of much debate and its role in the development of the disease and its unique sequence spanning the breakpoint region make it an ideal target for immunotherapy. (surrey.ac.uk)
  • Chen Y, Li D, Li S. The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. (umassmed.edu)
  • Recently, we definitively proved that targeting the tetramerization of BCR/ABL mediated by the N-terminal coiled-coil domain (CC) using competitive peptides, representing the helix-2 of the CC, represents a valid therapeutic approach for treating Ph+ leukemia. (uni-frankfurt.de)
  • Pharmacological targeting of c-Abl and its downstream effector pathways may, therefore, represent a novel therapeutic approach to blocking TGF-β-dependent fibrotic processes. (elsevier.com)
  • 30% absolute reduction in Philadelphia chromosome-positive metaphases at 12 weeks cross over to arm I after a 1-week washout period. (clinicaltrials.gov)
  • NEW YORK--( BUSINESS WIRE )--Pfizer Inc. (NYSE:PFE) today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indication for BOSULIF ® (bosutinib) to include adult patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). (businesswire.com)
  • For the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). (pdr.net)
  • New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia," Blood , vol. 76, no. 9, pp. 1819-1824, 1990. (hindawi.com)
  • A drug used to treat certain types of chronic myelogenous leukemia (CML) that are Philadelphia chromosome positive. (cancer.gov)
  • The BCR/ABL fusion protein is the hallmark of Philadelphia Chromosome positive (Ph+) leukemia. (uni-frankfurt.de)
  • Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. (nih.gov)
  • Some patients who have chronic myelogenous leukemia have Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). (rxwiki.com)
  • Bosutinib is a prescription medicine used to treat adults who have a certain type of leukemia called Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) who no longer benefit from or did not tolerate other treatment. (rxwiki.com)
  • Other patients have Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). (rxwiki.com)
  • It is also approved for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). (rxwiki.com)
  • newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. (rxwiki.com)
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatment. (rxwiki.com)
  • Phase II trial of hyper CVAD and dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia. (springer.com)
  • First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. (springer.com)
  • Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate. (springer.com)
  • How we approach Philadelphia chromosome-positive acute lymphoblastic leukemia in children and young adults. (harvard.edu)
  • Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. (harvard.edu)
  • Determine the major molecular response rate prior to crossover, as determined by BCR-ABL transcripts in blood during treatment using quantitative reverse transcriptase polymerase chain reaction, in patients treated with these drugs. (clinicaltrials.gov)
  • Many of the leukemia terms have undergone name changes as immunophenotypic and molecular biological techniques have made diagnosis more precise. (nih.gov)
  • Polycythemia Vera Study Group includes absence of the Philadelphia Chromosome, using molecular studies for BCR-ABL. (clinicaladvisor.com)
  • Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction)," Blood , vol. 88, no. 7, pp. 2410-2414, 1996. (hindawi.com)
  • Chronic myeloid leukemia with e19a2 BCR-ABL1 transcripts and marked thrombocytosis: the role of molecular monitoring," Case Reports in Hematology , vol. 2012, Article ID 458716, 3 pages, 2012. (hindawi.com)
  • Despite the outstanding results of imatinib in the chronic phase of CML, cases of treatment failure have been reported, resulting in hetero-geneous molecular response. (scirp.org)
  • Quintas-Cardama, A., Cortes, J. (2008) Molecular biol-ogy of bcr-abl1-positive chronic myeloid leukemia. (scirp.org)
  • Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative chronic myelogenous leukemia. (annals.org)
  • Interestingly, elevated expression of Hes1 was found in two of five samples of Fip1-like1 platelet-derived growth factor receptor-α (FIP1L1-PDGFA)-positive myeloid neoplasms associated with eosinophilia. (nih.gov)
  • Chronic myelogenous leukemia (CML) /myeloproliferative neoplasms (MPN). (springer.com)
  • Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. (harvard.edu)
  • Leukemia starts in blood-forming tissues such as the bone marrow. (medlineplus.gov)
  • When you have leukemia, your bone marrow makes large numbers of abnormal cells. (medlineplus.gov)
  • Chronic phase, where less than 10% of cells in the blood and bone marrow are blast cells (leukemia cells). (medlineplus.gov)
  • The prognosis is less favourable if there is a large number of leukemia cells in the bone marrow. (cancer.ca)
  • Having areas of bone damage from growth of leukemia cells at the time of diagnosis is also a less favourable prognostic factor. (cancer.ca)
  • Chronic myelogenous leukemia (CML) is a rare blood cancer, which begins in the bone marrow, but often moves into the blood. (businesswire.com)
  • When mouse bone marrow cells expressing Bcr-Abl are placed in short-term cultures selectively designed to support the outgrowth of pre-B cells, only those lacking one or two Arf alleles can initiate lympholeukemias when inoculated into immunocompetent, syngeneic recipient mice. (pnas.org)
  • Although CML and Ph + ALL are triggered by very similar BCR-ABL oncoproteins, durable responses of Ph + ALL patients to imatinib therapy are uncommon ( 11 ), and these patients, both pediatric and adult, receive other conventional combinational chemotherapy and/or bone marrow transplants to stem their disease. (pnas.org)
  • This review examines the role of nilotinib, an oral second-generation TKI, in the treatment of Philadelphia positive CML. (dovepress.com)
  • Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses," Health Technology Assessment , vol. 16, no. 42, pp. 1-277, 2012. (hindawi.com)
  • Assess whether retroviral transduction of mobilized PBSC progenitors determines the contribution of malignant Ph positive progenitors contaminating the graft to relapse after transplantation in these patients. (clinicaltrials.gov)
  • Marqibo is a vinca alkaloid indicated for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies (Acrotech, 2020). (aetna.com)
  • In 2012, Marqibo (vincristine sulfate liposome injection) was approved by the U.S. Food and Drug Administration for the treatment adult patients with Philadelphia chromosome‐negative (Ph‐) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti‐leukemia therapies. (aetna.com)
  • Nearly all patients with lymphoid blast crisis and Ph-positive ALL had a relapse within six months. (nih.gov)
  • For the treatment of newly diagnosed chronic phase Ph+ CML. (pdr.net)
  • Additionally, the potential expansion of the approved use of BOSULIF to include first-line therapy expands the treatment options for adult patients with newly diagnosed chronic myelogenous leukemia. (pfizer.com)
  • The Type II Variation application for BOSULIF for adults with newly diagnosed chronic phase Ph+ CML was based on results from BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment), a randomized multicenter, multinational, open-label, Phase 3, head-to-head study of BOSULIF 400 mg versus imatinib 400 mg, a current standard of care. (pfizer.com)
  • Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial," Journal of Clinical Oncology , vol. 30, no. 28, pp. 3486-3492, 2012. (hindawi.com)
  • Bosutinib versus imatinib in newly diagnosed chronic phase phronic myeloid leukemia-BELA trial: 24-month follow-up," Blood , vol. 118, abstract 455, 2011, ASH Annual Meeting Abstracts. (hindawi.com)
  • BELA trial update: bosutinib (BOS) versus imatinib (IM) in patients (pts) with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) after 30 months of follow-up," Journal of Clinical Oncology , vol. 30, abstract 6512, 2012. (hindawi.com)
  • Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia," The New England Journal of Medicine , vol. 362, no. 24, pp. 2260-2270, 2010. (hindawi.com)
  • Acute myelogenous leukemia (AML) is a hematologic malignancy characterized by a block in cellular differentiation and aberrant growth of myeloid precursor cells. (aacrjournals.org)
  • This translocation creates the BCR-ABL fusion gene, which leads to the development of CML. (cancer.ca)
  • Chronic myeloid leukaemia (CML) results from a translocation between chromosomes 9 and 22 which generates the BCR/ABL fusion oncopro-tein. (scirp.org)
  • However, disease progression may be mediated by other mechanisms that render tumor cells independent of BCR-ABL. (aacrjournals.org)
  • The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. (sciencemag.org)
  • F-18 16 alpha-fluoroestradiol is actively taken up in tumor cells expressing the estrogen receptor (ER), allowing visualization of ER-positive tumor cells with positron emiision tomography (PET). (cancer.gov)
  • In addition, this agent is able to sensitize FACT-positive tumor cells to the cytotoxic effects of other chemotherapeutic agents. (cancer.gov)
  • Single-agent therapy for relapsed/refractory Philadelphia-positive ALL refractory to TKIs (NCCN, 2020b). (aetna.com)
  • Faderl, S., Rai, K., Gribben, J., et al (2006) Phase II study of single-agent bortezomib for the treatment of pa-tients with fludarabine-refractory B-cell chronic lym-phocytic leuk cancer. (scirp.org)
  • E ) qRT-PCR analysis of BCR-ABL mRNA level in CD45 + cells engrafted in BM at 12 weeks. (jci.org)
  • Proliferation of MO7 (growth factor-dependent) and BV173 (bcr-abl-dependent) cells, but not that of NB4 and HL-60 (growth factor-independent) cells, was also inhibited, even though a specific downregulation of GAP was observed in each cell line, as analyzed by either or both mRNA and protein expression. (rupress.org)
  • Using chronic myelogenous leukemia (CML) as a model, we tested the hypothesis that cytokine-independent growth of leukemia cells results from aberrant activation of cytokine signaling pathways. (nih.gov)
  • Reconstitution experiments in non-hematopoietic cells show that STAT5 activation by BCR-ABL occurs independent of cytokines. (nih.gov)
  • Leukemia is a term for cancers of the blood cells. (medlineplus.gov)
  • This protein allows the leukemia cells to grow out of control. (medlineplus.gov)
  • Determine whether priming with cyclophosphamide and filgrastim (G-CSF) increases the fraction of benign Philadelphia chromosome negative hematopoietic progenitors in peripheral blood stem cells (PBSC) and reduces the incidence of persistent or recurrent leukemia after autologous transplantation with mobilized PBSC in these patients. (knowcancer.com)
  • To demonstrate this potential, IM-resistant cells were found in chronic myelogenous leukemia patients with continuous BCR-ABL gene expression but undetectable BCR-ABL protein expression. (aacrjournals.org)
  • These cells were unresponsive to IM and acquired BCR-ABL-independent signaling characteristics. (aacrjournals.org)
  • About 95% of adults with CML have leukemia cells with the Ph chromosome. (cancer.ca)
  • Higher levels of LDH may mean that there is tissue damage or there are leukemia cells, or blasts, in the blood. (cancer.ca)
  • This means a decrease to 35% or less of the leukemia cells with the Ph chromosome. (cancer.ca)
  • To identify regulators of primitive chronic myeloid leukemia (CML) cells, we performed a high-content cytokine screen using primary CD34 + CD38 low chronic phase CML cells. (haematologica.org)
  • Focusing on novel positive regulators of primitive CML cells, the myostatin antagonist myostatin propeptide gave the largest increase in cell expansion and was chosen for further studies. (haematologica.org)
  • In the present study, we discovered a positive feedback loop between BCR-ABL and protein arginine methyltransferase 5 (PRMT5) in CML cells. (jci.org)
  • Blood 98:2887-2893, 2001), this study demonstrated the expression of MHC-peptide complexes on the surface of CML cells and the presence of tetramer-positive CTL activity in CML patients positive for these two HLA alleles. (surrey.ac.uk)
  • This is the first demonstration that altering the location of plasmid expressed Bcr-Abl can kill leukemia cells. (pubmedcentralcanada.ca)
  • Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib. (pnas.org)
  • Leukemia is a type of cancer found when blood cells divide rapidly. (rxwiki.com)
  • It works by targeting the Bcr-Abl protein found on leukemia cells. (rxwiki.com)
  • By binding to the Bcr-Abl protein, bosutinib prevents the growth of cancer cells. (rxwiki.com)
  • Bcr-Abl makes leukemia cells divide more rapidly. (rxwiki.com)
  • This gene can also make leukemia cells resistant to certain types of treatment. (rxwiki.com)
  • Dasatinib is a prescription medication used to treat certain types of leukemia (cancers of the white blood cells). (rxwiki.com)
  • Leukemia is a cancer that forms in the blood cells. (rxwiki.com)
  • Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myeloid leukemia (AML). (bloodjournal.org)
  • Kwee, J.K., Luque, D.G., dos Santos Ferreira, A.C., et al (2008) Modulation of reactive oxygen species by anti-oxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation. (scirp.org)
  • Lineage switch is a very rare event in blastic crisis of chronic myelogenous leukemia (CML-BC). (biomedsearch.com)
  • In summary, SHP1 levels are low in healthy volunteers and that they are up-regulated in patients with chronic phase disease and decrease as CML transitions into the accelerated and blastic phases. (aacrjournals.org)
  • Tumour antigen-targeted immunotherapy for chronic myeloid leukaemia: is it still viable? (surrey.ac.uk)
  • Various immunotherapy strategies have been trialled in several leukaemias including chronic myeloid leukaemia (CML) and in general, these have been aimed at targeting tumour-associated antigens (TAA). (surrey.ac.uk)
  • Rajappa S, Uppin SG, Raghunadharao D, Rao IS, Surath A. Isolated central nervous system blast crisis in chronic myeloid leukaemia. (springer.com)
  • Bosutinib (BOS) versus imatinib (IM) in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) in the BELA trial: 18-month follow-up," Journal of Clinical Oncology , vol. 29, supplement, abstract 6509, 2011. (hindawi.com)
  • abstract = "The nonreceptor protein tyrosine kinase c-Abl regulates cell proliferation and survival. (elsevier.com)
  • The levels of SHP1, GAPDH, and c-ABL were studied using real-time polymerase chain reaction (PCR). (aacrjournals.org)
  • If approved, the addition of MYLOTARG to standard chemotherapy will provide an important new treatment option for patients with acute myeloid leukemia who would typically be treated with chemotherapy alone. (pfizer.com)