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Mechanisms of Transformation by the BCR/ABL Oncogene

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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.

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  1. Department of Adult Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Martin Sattler & James D. Griffin

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Sattler, M., Griffin, J.D. Mechanisms of Transformation by the BCR/ABL Oncogene. Int J Hematol 73, 278–291 (2001). https://doi.org/10.1007/BF02981952

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