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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4780-4787. Prepublished online as a Blood First Edition Paper on February 26, 2008; DOI 10.1182/blood-2007-08-109074. This Article Full Text (PDF) All Versions of this Article: blood-2007-08-109074v1 111/9/4780    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Contassot, E. Articles by French, L. E Search for Related Content PubMed PubMed Citation Articles by Contassot, E. Articles by French, L. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 23, 2007 Accepted January 15, 2008 Resistance to FasL and TRAIL-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and cFLIP expression Emmanuel Contassot, Katrin Kerl, Stephanie Roques, Ryan Shane, Olivier Gaide, Marc Dupuis, Alain H Rook, and Lars E French* Department of Dermatology, Zurich University Hospital, Zurich, Switzerland Department of Pathology and Immunology, Louis-Jeantet Skin Cancer Laboratory, University Medical Center, Geneva, Switzerland Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States Department of Dermatology, Geneva University Hospital, Geneva, Switzerland Topotarget Switzerland, Lausanne, Switzerland * Corresponding author; email: lars.french{at}usz.ch. Due to the low proliferative potential of tumor cells in Sezary's Syndrome (SzS) patients, their accumulation has been suggested to be due to defective regulation of apoptosis. We analyzed the sensitivity to soluble Fas-ligand (FasL) and TRAIL, two members of the TNF-superfamily in SzS patients PBL. In comparison to healthy donors, CD4+ cells from SzS patients were completely resistant to FasL in 9/16 cases. Of these 9 FasL-resistant cases, 4 revealed a loss in Fas (CD95) expression, whereas the remaining 5 exhibited normal or enhanced Fas expression. In the latter 5 cases, the apoptosis inhibitor cFLIP was overexpressed in CD4+/CD26- tumor cells when compared to CD4+/CD26- cells from Fas-expressing FasL-sensitive patients and healthy donors. Furthermore, resistance to TRAIL and tumor cell-restricted loss of TRAIL-receptor 2 were observed in 16/16 SzS PBL. Interestingly, resistance to FasL could be overcome by the use of an hexameric FasL or upon exposure of SzS cells to IFN- or -, the latter by an increase of Fas expression. Our data on primary SzS lymphocytes reveal frequent resistance to apoptosis induced by FasL and TRAIL which may contribute to their accumulation in SzS patients and be relevant at a therapeutic level. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.-D. Klemke, D. Brenner, E.-M. Weiss, M. Schmidt, M. Leverkus, K. Gulow, and P. H. Krammer Lack of T-Cell Receptor-Induced Signaling Is Crucial for CD95 Ligand Up-regulation and Protects Cutaneous T-Cell Lymphoma Cells from Activation-Induced Cell Death Cancer Res., May 15, 2009; 69(10): 4175 - 4183. [Abstract] [Full Text] [PDF]

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