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 non-malignant cells makes this messenger RNA an ideal candidate for antisense strategies in CML. To inhibit the expression of the bcr-abl gene, and to try to eradicate Philadelphia-positive cells, different methods can be used: 1) the introduction into the cells of antisense oligonucleotides, 2) the use of specific ribozymes, or 3) the transduction, using retroviral vectors, of stably integrated sequences coding for antisense RNA. Each of these approaches has potential advantages and drawbacks that are discussed below. Although many data emerge that support the use of anti-bcr-abl antisense molecules in CML, numerous questions remain to be completely answered before the most efficient strategy can be designed, either for in vitro or in vivo purposes.