Mechanisms of transformation by the BCR/ABL oncogene.
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 multiple 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 clinical intervention with specific signal transduction inhibitors such as STI-571 in CML.
Sattler
M
M
Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Griffin
J D
JD
D001549:Benzamides; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D010677:Philadelphia Chromosome; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000502:physiology
D001549:Benzamides; D004791:Enzyme Inhibitors; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl