Retrovirally transduced antisense sequences stably suppress P210BCR-ABL expression and inhibit the proliferation of BCR/ABL-containing cell lines.

摘要: There is now strong evidence that the BCR-ABL gene product of Philadelphia chromosome (P210) plays a crucial role in pathogenesis chronic myeloid leukemia (CML). We have previously shown introduction antisense oligonucleotides into K562 cells could transiently block expression P210 and specifically inhibit cellular growth culture. In this report, we describe use retroviral vector to introduce selected sense sequences, first murine B10 cells, rendered interleukin-3 (IL-3) independent by transfection second cells. The transcripts generated under control MoMLV promoter killed absence IL-3 inhibited almost completely. sequences led dramatic reduction increased their doubling time more than twofold. This effect was not reversed addition exogenous culture medium. Control HeLa or HL60 infected with same constructs did show any change proliferation rate, despite abrogation normal BCR products. Rather unexpectedly, suppression lethal showing such cell line does rely entirely on for surviving, but depends it as far properties are concerned. conclude approach can successfully achieve stable oncogenic protein may be used study further mechanisms which transforming fresh CML bone marrow cultures remains assessed before tell whether technique selective leukemic hematopoiesis vitro.