Antisense oligonucleotides complementary to immunoglobulin sequences of BCL-2/immunoglobulin fusion transcript induce apoptosis of t(14;18) lymphoma cells

Antisense oligodeoxyribonucleotides directed at the bcl-2 translational sta rt site downregulate bcl-2 and inhibit growth of the t(14;18)-positive lymp homa line WSU-FSCCL. Non-specific downregulation of bcl-2 expression is exp ected to be toxic to normal cells as well. The t(14;18) translocation resul ts in a fusion transcript containing the entire bcl-2 coding sequence with a 3' breakpoint fused to the immunoglobulin J(H) region and the c(mu) heavy chain. We postulated that these immunoglobulin sequences would he a specif ic target for downregulation of the fusion gene. Here, we have demonstrated that antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences downregulate bcl-2 protein expression and induce apoptosis of WSU -FSCCL cells. inhibiting growth of malignant cells by targeting non-oncogen ic sequences other than breakpoints of fusion transcripts expands the poten tial for tumour-specific genetic manipulation.