Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line

Susanna Morelli, Angela Alama, Alessandro Quattrone, Lei Gong, Elena Copreni, Gianfranco Canti, Angelo Nicolin

Research output: Contribution to journalArticle

Abstract

Most human follicular B-cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of BCL-2 protein expression, endowing cells with survival advantage. Although early BCL-2 overexpression is definitely responsible for immortalization/transformation, its exact role in the overt transformation as well as in the maintenance of the tumor phenotype is not known. The capacity of oligodeoxynucleotides (ODN) to modulate gene expression specifically has been exploited to downregulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B-cell lymphoma line by the use of sense ODN or antisense ODN designed to encompass the unique nucleotide sequence in the fusion region of the hybrid transcript. The specific downregulation of the bcl-2 transcript and of the relevant BCL-2 protein in the treated cells activated programed cell death and inhibited growing cells. The antitumor activity was restricted to the DHL-4 cell line carrying the specific nucleotide sequence at the bcl-2/IgH joining region. Thus, DHL-4 lymphoma cells derived from the acute phase of human follicular B-cell lymphoma, although endowed with additional activated oncogenes, were growth inhibited by bcl-2 downregulation in a genetically restricted fashion. The biological activity was exerted exclusively by ODNs synthesized in the sense orientation. The sense ODNs have been proposed to anneal the hybrid bcl-2/IgH antisense RNA as identified in this study.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalAnti-Cancer Drug Design
Volume11
Issue number1
Publication statusPublished - Jan 1996

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Keywords

  • Apoptosis
  • B-cell lymphoma
  • bcl-2 gene
  • Oligodeoxynucleotides
  • t(14;18)

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Morelli, S., Alama, A., Quattrone, A., Gong, L., Copreni, E., Canti, G., & Nicolin, A. (1996). Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line. Anti-Cancer Drug Design, 11(1), 1-14.