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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.