Efficacy of treatment with antisense oligonucleotides complementary to immunoglobulin sequences of bcl-2/immunoglobulin fusion transcript in a t(14;18) human lymphoma-scid mouse model

In t(14;18)-positive lymphoma cells, bcl-2 is expressed from a fusion mRNA. transcript containing the full coding sequence of bcl-3 and 3' immunoglobu lin sequences. We reported previously that antisense oligodeoxyribonucleoti des directed at the bcl-2 translational start site, as well as those target ed to immunoglobulin sequences 3' of the translocation breakpoint, do,vn-re gulate bcl-2 and inhibit growth of the t(14;18)-positive lymphoma line WSU- FSCCL in vitro. We have developed a scid mouse model with this human cell l ine and demonstrate that antisense oligodeoxyribonucleotides targeted to im munoglobulin c, sequences down-regulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells in vivo. This leads to prolonged survival of the mice. Targeting non-oncogenic sequences outside of the breakpoints of f usion transcripts may be a clinically useful therapeutic strategy.