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 start site downregulate bcl‐2 and inhibit growth of the t(14;18)‐positive lymphoma line WSU‐FSCCL. Non‐specific downregulation of bcl‐2 expression is expected to be toxic to normal cells as well. The t(14;18) translocation results in a fusion transcript containing the entire bcl‐2 coding sequence with a 3′ breakpoint fused to the immunoglobulin JH region and the cμ heavy chain. We postulated that these immunoglobulin sequences would be a specific target for downregulation of the fusion gene. Here, we have demonstrated that antisense oligodeoxyribonucleotides targeted to immunoglobulin cμ sequences downregulate bcl‐2 protein expression and induce apoptosis of WSU‐FSCCL cells. Inhibiting growth of malignant cells by targeting non‐oncogenic sequences other than breakpoints of fusion transcripts expands the potential for tumour‐specific genetic manipulation.