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

Abstract

Summary. 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 H breakpoint fused to the immunoglobulin J H region and the c m 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 c m 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 tumourspecific genetic manipulation.

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Bortezomib Sensitizes Non–Hodgkin's Lymphoma Cells to Apoptosis Induced by Antibodies to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Receptors TRAIL-R1 and TRAIL-R2

“…The DoHH2 and WSU-FSCCL cell lines were maintained in logphase growth in RPMI 1640 + 10% heat-inactivated fetal bovine serum, 2 mmol/L glutamine, 100 units/mL penicillin, and 100 g/mL streptomycin, as before (43).…”