Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma

Ngoc L. Toomey, Vadim V. Deyev, Charles Wood, Lawrence H. Boise, Duncan Scott, Lei Hua Liu, Lisa Cabral, Eckhard R. Podack, Glen N. Barber, William J. Harrington

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Gammaherpes viruses are often detected in lymphomas arising in immunocompromised patients. We have found that Azidothymidine (AZT) alone induces apoptosis in Epstein Barr Virus (EBV) positive Burkitt's lymphoma (BL) cells but requires interferon alpha (IFN-α) to induce apoptosis in Human Herpes Virus Type 8 (HHV-8) positive Primary Effusion Lymphomas (PEL). Our analysis of a series of AIDS lymphomas revealed that IFN-α selectively induced very high levels of the Death Receptor (DR) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HHV-8 positive PEL lines and primary tumor cells whereas little or no induction was observed in primary EBV + AIDS lymphomas and EBV - Burkitt's lines. AZT and IFN-α mediated apoptosis in PEL was blocked by stable overexpression of dominant negative Fas Associated Death Domain (FADD), decoy receptor 2 (DcR2), soluble TRAIL receptor fusion proteins (DR-4 and DR-5) and thymidine. Trimeric TRAIL (in place of IFN-α) similarly synergized with AZT to induce apoptosis in HHV-8 positive PEL cells. This is the first demonstration that IFN-α induces functional TRAIL in a malignancy that can be exploited to effect a suicide program. This novel antiviral approach to Primary Effusion lymphomas is targeted and may represent a highly effective and relatively non-toxic therapy.

Original languageEnglish (US)
Pages (from-to)7029-7040
Number of pages12
JournalOncogene
Volume20
Issue number48
DOIs
StatePublished - Oct 25 2001

Keywords

  • Apoptosis
  • Epstein Barr virus
  • FADD
  • Human Herpes Virus Type 8
  • Lymphoma
  • TRAIL

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Toomey, N. L., Deyev, V. V., Wood, C., Boise, L. H., Scott, D., Liu, L. H., Cabral, L., Podack, E. R., Barber, G. N., & Harrington, W. J. (2001). Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma. Oncogene, 20(48), 7029-7040. https://doi.org/10.1038/sj.onc.1204895