The Bcr gene, mapping on chromosome 22, was initially identified on the basis of its fusion with the c-Abl proto-oncogene on chromosome 9 resulting in the generation of the Philadelphia chromosome in 90-95% of patients with chronic myelogenous leukemia (CML). The Bcr gene encodes for the Breakpoint cluster region protein (Bcr). A consequence of this translocation is the generation of a Bcr/c-Abl mRNA encoding an activated c-Abl protein kinase. The Bcr gene has been shown to encode a 160 kDa GTPase-activating protein (GAP) specific for the Ras-related GTP-binding protein, Rac 1 p21. While it has been speculated that the Bcr protein may also stimulate Rac 2 p21 GTPase activity, it has no effect on Ras p21 or Rho p21 GTPases. It is of interest that the GAP domain of Bcr maps outside of the region that remains on chromosome 22 (Philadelphia chromosome) in CML.