Chronic Myeloid Leukemia: Biology of Advanced Phase

  • Junia V. Melo
  • David J. Barnes
Part of the Hematologic Malignancies book series (HEMATOLOGIC)


Chronic myeloid leukemia (CML) usually starts with an indolent chronic phase characterized by the overproduction of mature granulocytes, but inevitably evolves to a terminal blastic phase in which excessive numbers of undifferentiated blasts are produced. The molecular mechanisms underlying disease progression are still very poorly understood. Whereas the BCR-ABL oncogene has a central role in disease etiology, it is not sufficient by itself to precipitate the transition to blast crisis. Other secondary genetic events are presumed to be essential for this process but the number required for blastic transformation is still unknown. Although various genetic abnormalities have been identified in blast crisis samples, the significance of these for disease progression is far from certain. Candidate genes, suggested by their induced cellular phenotype, have been investigated, usually in in vitro models of CML. Several of these genes have also proven to have abnormal expression or activity in small numbers of CML blast crisis samples. At the cytogenetic level, disease progression in CML is often accompanied by the appearance of nonrandom chromosomal abnormalities. These are the microscopically visible manifestations of an underlying genomic instability and increased tolerance of genetic aberrations. Here we summarize the current state of knowledge concerning the biology of advanced phase CML.


Chronic Myeloid Leukemia Nucleotide Excision Repair Ataxia Telangiectasia Mutate Chronic Myeloid Leukemia Patient Blast Crisis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Berlin Heidelberg 2007

Authors and Affiliations

  • Junia V. Melo
    • 1
  • David J. Barnes
    • 1
  1. 1.Department of Haematology, Faculty of Medicine, Imperial College LondonHammersmith HospitalLondonUK

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