BCR-ABL: a multi-faceted promoter of DNA mutation in chronic myelogeneous leukemia.
The role of the BCR-ABL oncogene in the progression of chronic myeloid leukemia (CML) to blast crisis (BC) is unknown. The appearance of chromosomal aberrations in patients with CML BC has led to many attempts to elucidate a mechanism whereby BCR-ABL affects DNA damage and repair. BCR-ABL-expressing cells have been found to accumulate genetic abnormalities, but the mechanism leading to this genomic instability is controversial. In this study, we review the effects of BCR-ABL on DNA repair mechanisms, centrosomes, checkpoint activation and apoptosis. BCR-ABL has diverse effects on these mechanisms, but which of these effects are necessary for the progression of CML to BC is still unresolved.
Burke
B A
BA
Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Carroll
M
M
D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*
D004273:DNA, Neoplasm; D016044:Fusion Proteins, bcr-abl
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