title: Chronic myeloid leukemia: why does it evolve from chronic phase to blast transformation?
abstract: Clinically chronic myeloid leukemia is a biphasic or triphasic disease that is usually diagnosed in the initial 'chronic', 'indolent' or 'stable' phase and then spontaneously evolves after some years into an advanced phase. This advanced phase can sometimes be subdivided into an earlier accelerated phase and a later blast phase or blast transformation--in about one-half of patients the chronic phase transforms unpredictably and abruptly to a blast phase, while in the other half of patients, the disease evolves somewhat more gradually, through an accelerated phase, which may last for months or years, before a blast phase ensues; this may have myeloblastic or lymphoblastic features. Although much is now known about the molecular biology of the disease, the molecular basis of disease progression is still obscure. The popular thinking has been that one or more probably a sequence of additional genetic events occurs in the BCR-ABL positive clone. When the critical combination of additional events is achieved, clinically definable transformation occurs. Here we review what is known of the mechanisms underlying the evolution of chronic myeloid leukemia from a chronic phase to a blast transformation.
authors.affiliation: Division of Hematology and Oncology, University of Massachusetts Medical School, Worcester, MA 01655, USA. tmughal@freenet.co.uk
authors.forename: Tariq I
authors.initials: TI
authors.lastname: Mughal
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
mesh_terms: D000818:Animals; D017209:Apoptosis; D005075:Biological Evolution; D001752:Blast Crisis; D003582:Cytogenetics; D048749:Cytokinesis; D004260:DNA Repair; D018450:Disease Progression; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053613:Janus Kinase 1; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010677:Philadelphia Chromosome; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013997:Time Factors
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D046988:Proteasome Endopeptidase Complex