Vaerman J L, Lewalle P, Martiat P
Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Stem Cells. 1993 Oct;11 Suppl 3:89-95. doi: 10.1002/stem.5530110921.
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.
费城染色体的bcr-abl基因产物（P210）在慢性粒细胞白血病（CML）发病机制中起关键作用，且非恶性细胞中不存在bcr-abl融合转录本，这使得该信使RNA成为CML反义策略的理想候选对象。为抑制bcr-abl基因的表达并试图根除费城染色体阳性细胞，可采用不同方法：1）将反义寡核苷酸导入细胞；2）使用特异性核酶；或3）利用逆转录病毒载体转导编码反义RNA的稳定整合序列。以下将讨论每种方法的潜在优缺点。尽管有许多数据支持在CML中使用抗bcr-abl反义分子，但在设计出最有效的体外或体内策略之前，仍有许多问题有待完全解答。
