TUMORIGENIC ACTIVITY OF THE BCR-ABL ONCOGENES IS MEDIATED BY BCL2

BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210(BCR-ABL ) and p190(ECR-ABL), are produced that are characteristic of chronic m yelogenous leukemia and acute lymphoblastic leukemia, respectively. Th eir role in the etiology of human leukemia remains to be defined. Tran sformed murine hematopoietic cells can be used as a model of BCK-ABL f unction since these cells can be made growth factor independent and tu morigenic by the action of the BCR-ABL oncogene. We show that the BCR- ABL oncogenes prevent apoptotic death in these cells by inducing a Bcl -2 expression pathway. Furthermore, BCR-ABL-expressing cells revert to factor dependence and nontumorigenicity after Bcl-2 expression is sup pressed. These results help to explain the ability of BCR-ABL oncogene s to synergize with c-myc in cell transformation.