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

Oncogene volume 20, pages 7029–7040 (2001)Cite this article

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.

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Acknowledgements

The authors wish to thank Drs Parkash Gill (University of Southern California) and Scott Kaufmann (Mayo clinic, Rochester, MN) for their helpful suggestions. This work was supported by grants CA82274 (WJ Harrington Jr and LH Boise), CA77837 (WJ Harrington Jr and LH Boise), CA86431 (GN Barber), CA80228 and CA39201 (ER Podack) from the National Institutes of Health.

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Author notes

  1. Ngoc L Toomey and Vadim V Deyev: N L Toomey and VV Deyev contributed equally to this work

Authors and Affiliations

  1. Department of Medicine, University of Miami School of Medicine, Miami, FL 33136, Florida, USA

    Ngoc L Toomey, Duncan Scott, Lei Hua Liu, Lisa Cabral & William J Harrington Jr

  2. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, Florida, USA

    Vadim V Deyev, Lawrence H Boise, Eckhard R Podack & Glen N Barber

  3. School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, NE 68588, USA

    Charles Wood

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  1. Ngoc L Toomey
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  2. Vadim V Deyev
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  3. Charles Wood
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  4. Lawrence H Boise
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  7. Lisa Cabral
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  9. Glen N Barber
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  10. William J Harrington Jr
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Correspondence to William J Harrington Jr.

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Toomey, N., Deyev, V., Wood, C. et al. Induction of a TRAIL mediated suicide program by interferon alpha in primary effusion lymphoma. Oncogene 20, 7029–7040 (2001). https://doi.org/10.1038/sj.onc.1204895

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