ANTISENSE INHIBITION OF P210 BCR-ABL IN CHRONIC MYELOID-LEUKEMIA

The evidence that the bcr-abl gene product (P210) of the Philadelphia chromosome plays a crucial role in the pathogenesis of chronic myeloid leukemia (CML), and the absence of the bcr-abl fused transcript in no n-malignant cells makes this messenger RNA an ideal candidate for anti sense strategies in CML. To inhibit the expression of the bcr-abl gene , and to try to eradicate Philadelphia-positive cells, different metho ds can be used: 1) the introduction into the cells of antisense oligon ucleotides, 2) the use of specific ribozymes, or 3) the transduction, using retroviral vectors, of stably integrated sequences coding for an tisense RNA. Each of these approaches has potential advantages and dra wbacks that are discussed below. Although many data emerge that suppor t the use of anti-bcr-abl antisense molecules in CML, numerous questio ns remain to be completely answered before the most efficient strategy can be designed, either for in vitro or in vivo purposes.