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Bcr-Abl and Signal Transduction

  • Daniela Cilloni
  • Giuseppe Saglio
Part of the Hematologic Malignancies book series (HEMATOLOGIC)

Abstract

The BCR-ABL oncogene is generated by the Philadelphia (Ph) chromosome translocation, fusing the BCR to the ABL gene. The Bcr-Abl fusion protein has constitutive and deregulated tyrosine kinase activity that is critical for transformation of hematopoietic cells. Different leukemia phenotypes are preferentially associated with the three fusion Bcr-Abl proteins (p190, p210, and p230) that may be expressed from the hybrid gene. Cells transformed by Bcr-Abl show activation of mitogenic signaling pathways, inhibition of apoptosis and altered cellular adhesion. CML is characterized by an inevitable progression from a chronic phase to an acute phase called blast crisis. Progression of the disease is related to the acquisition of additional genetic alterations probably associated with genomic instability. This can be a consequence of Bcr-Abl activation or may even represent an ancestral stem cell defect preceding the acquisition of the Ph-chromosome translocation, as recent observations seem to suggest. However, the mechanisms responsible for Bcr-Abl rearrangement remain elusive, although the chromosomal translocation seems to occur relatively frequently in the general population, as evidenced by the detection of rare BCR-ABL fusion transcripts in the leukocytes of healthy individuals.

Keywords

Chronic Myelogenous Leukemia Chronic Myeloid Leukemia Cell Interferon Consensus Sequence Binding Protein Leukemia Phenotype Major Breakpoint Cluster Region 
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

  • Daniela Cilloni
    • 1
  • Giuseppe Saglio
    • 1
  1. 1.Department of Clinical and Biological Sciences of the University of TurinSan Luigi HospitalOrbassano-TorinoItaly

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