The BCR-ABL oncogene is generated by the Philadelphia chromosome (Ph) translocation,
fusing the BCR gene to the ABL gene. The BCR-ABL fusion protein has elevated ABL
tyrosine kinase activity that is critical for transformation of hematopoietic cells. Chronic
myelogenous leukemia (CML) cells transformed by BCR-ABL show reduced growth factor
requirements and apoptosis, as well as enhanced viability and altered adhesion. The
elevated ABL kinase activity leads to chronic activation of signaling pathways that are …

Since its introduction less than 3 years ago, imatinib mesylate (STI571) has altered the
entire approach to the therapy of patients with chronic myeloid leukemia (CML). In addition
to its impact on clinical practice, imatinib has also increased the focus of basic and
translational CML research on enhancing the cellular effects of imatinib and preventing and
overcoming resistance to the drug. Here, I summarize some recent advances in our
understanding of the regulatory and signaling mechanisms of Bcr-Abl, with an emphasis on …

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 …