THE REPRESSION OF APOPTOSIS BY ACTIVATED ABL ONCOGENES IN CHRONIC MYELOGENOUS LEUKEMIA

The formation of the unique fusion gene, bcr-abl, and the resultant in crease in abl tyrosine kinase activity, is seen as the major driving f orce in the initiation of chronic myelogenous leukaemia (CML). The der egulation of abl tyrosine kinase activity, brought about by the bindin g of a portion of the Bcr molecule to the SH2 regulatory domain of abl , appears to play a role in promoting resistance to drug-induced apopt osis. Thus the large increase in mature myeloid cells seen in CML coul d be the direct result of the suppression of apoptosis by the bcr-abl fusion protein. The role and contribution of apoptosis in the progress ion of CML and the possible role of antisense oligonucleotides to the bcr-abl gene as therapeutic agents is discussed.