The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway

BCR-ABL is a deregulated tyrosine kinase that is expressed in Philadelphia chromosome (Ph(1)) positive human leukemias, When expressed in hematopoietic cells, BCR-ABL causes cytokine independent proliferation, induces tumorigenic growth and prevents apoptosis in response to cytokine deprivation or DNA damage, One mechanism by which BCR-ABL signals in cells is by activating the small guanine nucleotide binding protein Ras, BCR-ABL-transformed cells have constitutively high levels of active, GTP-bound Ras, Here we use 32D cells that inducibly express a dominant negative Ras protein to define the Ras requirements in BCR-ABL-transformed cells, Dominant negative Ras inhibits BCR-ABL-mediated Ras activation, and induces cell death by an apoptotic mechanism, Therefore, BCR-ABL inhibits apoptosis through activation of a Ras-dependent signaling pathway.