The involvement of Bcr in leukemias with the Philadelphia chromosome.
In this review, the role of Bcr sequences within Bcr-Abl and the role of the Bcr protein itself in leukemias with the Philadelphia chromosome are discussed. An overview of the oncogenic effects of Bcr-Abl is presented together with Bcr-Abl's effects on several signal transduction pathways. Bcr sequences within Bcr-Abl are known to have an important function in transducing Bcr-Abl's oncogenic signal, yet the role of the Bcr protein encoded by the normal allele is not known. However, several recent findings suggest that Bcr is a conditional negative regulator of Bcr-Abl. From these findings, my colleagues and I have developed a molecular model of the early stage (benign phase) of chronic myelogenous leukemia in which the Bcr protein antagonizes the oncogenic effects of Bcr-Abl.
Arlinghaus
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Department of Molecular Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
D000818:Animals; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D016313:Genes, abl; D011905:Genes, ras; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D016315:Proto-Oncogene Proteins c-abl; D051562:Proto-Oncogene Proteins c-bcr; D015398:Signal Transduction
D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr