Progress in hematology

International Journal of Hematology

, Volume 73, Issue 3, pp 278-291

Mechanisms of Transformation by the BCR/ABL Oncogene

  • Martin SattlerAffiliated withDepartment of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
  • , James D. GriffinAffiliated withDepartment of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School Email author 

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Abstract

The Philadelphia chromosome generates a chimeric oncogene in which the BCR and c-ABL genes are fused. The product of this oncogene, BCR/ABL, has elevated ABL tyrosine kinase activity, relocates to the cytoskeleton, and phosphorylates mul-tiple cellular substrates. BCR/ABL transforms hematopoietic cells and exerts a wide variety of biological effects, including reduction in growth factor dependence, enhanced viability, and altered adhesion of chronic myelocytic leukemia (CML) cells. Elevated tyrosine kinase activity of BCR/ABL is critical for activating downstream signal transduction and for all aspects of transformation.This review will describe mechanisms of transformation by the BCR/ABL oncogene and opportunities for clin-ical intervention with specific signal transduction inhibitors such as STI-571 in CML.

Key words

BCR/ABL Signal transduction Chronic myelogenous leukemia