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 J(H) region and the c mu 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(mu) 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.
Smith
M R
MR
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. m_smith@fccc.edu
Xie
T
T
Zhou
Z Z
ZZ
Joshi
I
I
D017209:Apoptosis / Q000276:immunology*; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008223:Lymphoma / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D007128:Immunoglobulin Fragments; D007144:Immunoglobulin J-Chains; D007148:Immunoglobulin mu-Chains; D016376:Oligonucleotides, Antisense; D015514:Oncogene Proteins, Fusion