Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 95% of patients with chronic myelogenous leukemia (CML) contain an abnormal chromosome termed the Philadelphia chromosome (Ph1). Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. The product of the fused BCR-ABL genes is a protein of about 2000 amino acids termed P210 BCR-ABL. Although the BCR-ABL protein can be routinely detected in blood cells from blast crisis CML patients by assaying for its activated tyrosine kinase activity, detection of P210 BCR-ABL in early stage CML patients (chronic phase) has not yet been possible (S. A. Maxwell et al., Cancer Res., 47: 1731, 1987). A procedure involving Western blotting with an anti-ABL monoclonal antibody was developed that allows detection of P210 BCR-ABL and P145 ABL in cells from chronic phase and blast crisis CML patients, but as expected only P145 ABL was found in normal white blood cells. Most chronic phase patients also contained one to two ABL proteins with a molecular weight of about 190,000. Interestingly, the ratio of BCR-ABL to ABL proteins increased in four blast crisis patients compared to 18 chronic phase patients. Also, one chronic phase patient analyzed on three separate occasions lacked P210 BCR-ABL and exhibited only the Mr 190,000 form. This assay should also be useful in other leukemias that express altered forms of the ABL protein.
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PMID:Detection of BCR-ABL proteins in blood cells of benign phase chronic myelogenous leukemia patients. 203 43

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome (Ph1) in more than 95% of these patients. The Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. In CML, the product of the fused BCR-ABL gene is typically a protein of approximately 2,000 amino acids termed P210 BCR-ABL. We have developed an assay for the BCR-ABL protein involving Western blotting of circulating white blood cells (WBC) with an anti-ABL monoclonal antibody that can detect P210 BCR-ABL and P145 ABL in peripheral blood cells from chronic phase Ph1-positive leukemia patients. This assay was used to analyze the BCR-ABL protein content of circulating WBC from CML patients before and after various treatments. In parallel to changes in percentages of Ph1-positive blood cells as determined by cytogenetic analyses of bone marrow samples, BCR-ABL protein expression in blood cells decreased or increased as patients entered remission or underwent relapse. Of interest, six Ph1-negative CML patients were BCR-ABL protein-positive. All except one had a rearrangement in the major breakpoint cluster region and that patient expressed P185 BCR-ABL and not P210. Our results indicate that the BCR-ABL Western blotting assay has clinical applications for both diagnosis and prospective evaluation of Ph1-positive and Ph1-negative CML patients.
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PMID:BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy. 820 87

Cell surface levels of the receptor tyrosine kinase P145(c-kit), the product of the c-kit proto-oncogens, in a panel of 80 primary adult acute myeloid leukaemia (AML) specimens collected at presentation were quantitated by immunofluorescence and flow cytometry, and compared with levels on CD34+ bone marrow cells from normal donors. Receptor levels on AML blast cells were extremely variable and were similar to, or less than, those on normal stem and progenitor cells. In general P145(c-kit) expression was higher on cells of immature phenotype (FAB M1 and M2). c-kit mRNA was quantitated by ribonuclease protection assay (RPA) and was shown to be correlated with cell surface protein expression (r=0.76; P<0.001). This indicates that ligand-mediated receptor internalisation or other mechanisms of increased protein turnover are not responsible for variations in the level of P145(c-kit) in AML specimens. Quantitative Southern blotting was used to examine c-kit gene copy number in 25 of these specimens and was found to be normal in all but one. Thus we have found little evidence of over-expression of c-kit in adult AML. mRNA for the c-kit ligand, Steel Factor (SLF) was also quantitated by RPA in these specimens. While SLF message was detectable (limit of detection approximately 10(4) copies per 10 microgram total RNA; equivalent to 1 copy per 100 cells) in 19% of cases, these specimens in general contained low levels of c-kit mRNA. Thus, an autocrine cycle involving c-kit and SLF does not appear to be a common feature of AML.
Leukemia 1996 Feb
PMID:Increased expression of c-Kit or its ligand Steel Factor is not a common feature of adult acute myeloid leukaemia. 863 38

The Philadelphia chromosome (Ph) is found in most chronic myelogenous leukemia (CML) patients. The bcr-abl oncoprotein (P210 or P185), the product of the fused bcr-abl gene produced by the Ph, is known to be the major factor in initiation and maintenance of the leukemic state in these types of leukemias. The authors have devised a Western blot test to detect and quantitate the bcr-abl oncoprotein in blood and bone marrow cells. The authors analyzed 1,155 peripheral blood samples from CML patients, for which there were same day Ph data, to determine if there was a correlation between bcr-abl protein levels and the percentage of Ph. A ratio of bcr-abl protein (P210 or P185) to normal abl protein (P145), the latter is ubiquitously expressed in all blood cells, has been established as a criterion for quantitating bcr-abl levels. The bcr-abl/abl protein ratio from 399 patient who were 100% Ph-positive had a mean of 2.47 (standard error [SE] of +/- 0.05); no false negatives were detected. A decreasing ratio was found in patients with decreasing percentages of Ph. The relationship between the ratio of bcr-abl/abl proteins to the percentage of Ph-positive cells was nearly linear in 392 patients with Ph percentages between 5% to 95% (r = 0.97, P < .001). For patients in remission with no detectable Ph, the bcr-abl/abl ratio had a mean of 0.01 (SE = 0 +/- 0.00). The level of bcr-abl expression in samples from peripheral blood and bone marrow also were compared. The results indicated that the amount of bcr-abl protein within peripheral blood is usually similar to that in marrow. In conclusion, quantitation of the bcr-abl oncoprotein in peripheral blood cells or marrow cells as measured by a Western blot assay provides reliable data for both diagnosis and monitoring patients with pH-chromosome positive leukemia.
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PMID:Comparison of bcr-abl protein expression and Philadelphia chromosome analyses in chronic myelogenous leukemia patients. 885 30

The tyrosine kinase activity of BCR-ABL fusion proteins plays an important role in the pathogenesis of leukemia that is for the Philadelphia chromosome (Ph1). Because nuclear c-ABL is regulated during the cell cycle through a specific interaction with the retinoblastoma protein (pRB), the possible interaction of BCR-ABL with pRB in Ph1-positive cell lines was investigated. P145 c-ABL as well as P190 and P210 BCR-ABL proteins interacted with pRB. Furthermore, c-ABL and BCR-ABL associated with both phosphorylated and nonphosphorylated forms of pRB. These findings suggest that BCR-ABL interferes with pRB function and thereby regulates cell growth.
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PMID:Interaction of BCR-ABL with the retinoblastoma protein in Philadelphia chromosome-positive cell lines. 907 15