I. Sanchezgarcia et G. Grutz, TUMORIGENIC ACTIVITY OF THE BCR-ABL ONCOGENES IS MEDIATED BY BCL2, Proceedings of the National Academy of Sciences of the United Statesof America, 92(12), 1995, pp. 5287-5291
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.