Tags

Type your tag names separated by a space and hit enter

Induction of a TRAIL-mediated suicide program by interferon alpha in primary effusion lymphoma.
Oncogene 2001; 20(48):7029-40O

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-alpha) 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-alpha 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-alpha 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-alpha) similarly synergized with AZT to induce apoptosis in HHV-8 positive PEL cells. This is the first demonstration that IFN-alpha 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.

Authors+Show Affiliations

Department of Medicine, University of Miami School of Medicine, Miami, Florida, FL 33136, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11704827

Citation

Toomey, N L., et al. "Induction of a TRAIL-mediated Suicide Program By Interferon Alpha in Primary Effusion Lymphoma." Oncogene, vol. 20, no. 48, 2001, pp. 7029-40.
Toomey NL, Deyev VV, Wood C, et al. Induction of a TRAIL-mediated suicide program by interferon alpha in primary effusion lymphoma. Oncogene. 2001;20(48):7029-40.
Toomey, N. L., Deyev, V. V., Wood, C., Boise, L. H., Scott, D., Liu, L. H., ... Harrington, W. J. (2001). Induction of a TRAIL-mediated suicide program by interferon alpha in primary effusion lymphoma. Oncogene, 20(48), pp. 7029-40.
Toomey NL, et al. Induction of a TRAIL-mediated Suicide Program By Interferon Alpha in Primary Effusion Lymphoma. Oncogene. 2001 Oct 25;20(48):7029-40. PubMed PMID: 11704827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of a TRAIL-mediated suicide program by interferon alpha in primary effusion lymphoma. AU - Toomey,N L, AU - Deyev,V V, AU - Wood,C, AU - Boise,L H, AU - Scott,D, AU - Liu,L H, AU - Cabral,L, AU - Podack,E R, AU - Barber,G N, AU - Harrington,W J,Jr PY - 2001/05/14/received PY - 2001/07/17/revised PY - 2001/08/02/accepted PY - 2001/11/13/pubmed PY - 2002/1/5/medline PY - 2001/11/13/entrez SP - 7029 EP - 40 JF - Oncogene JO - Oncogene VL - 20 IS - 48 N2 - 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-alpha) 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-alpha 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-alpha 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-alpha) similarly synergized with AZT to induce apoptosis in HHV-8 positive PEL cells. This is the first demonstration that IFN-alpha 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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11704827/Induction_of_a_TRAIL_mediated_suicide_program_by_interferon_alpha_in_primary_effusion_lymphoma_ L2 - http://dx.doi.org/10.1038/sj.onc.1204895 DB - PRIME DP - Unbound Medicine ER -