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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 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 Citation Map 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 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. Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sézary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expression Emmanuel Contassot*,1, Katrin Kerl*,1, Stéphanie Roques2,3, Ryan Shane4, Olivier Gaide2,3, Marc Dupuis5, Alain H. Rook4, and Lars E. French1 1 Department of Dermatology, Zürich University Hospital, Zürich, Switzerland; 2 Louis-Jeantet Skin Cancer Laboratory, Department of Pathology and Immunology, University Medical Center, Geneva, Switzerland; 3 Department of Dermatology, University Hospital, Geneva, Switzerland; 4 Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia; and 5 Topotarget Switzerland, Lausanne, Switzerland Because of the low proliferative potential of tumor cells in patients with Sézary syndrome (SzS), their accumulation has been suggested to be due to defective regulation of apoptosis. We analyzed the sensitivity to soluble Fas-ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), 2 members of the TNF superfamily in peripheral blood leukocytes (PBL) from patients with SzS. Compared with healthy donors, CD4+ cells from patients with SzS were completely resistant to FasL in 9 of 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 compared with 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 of 16 SzS PBLs. It is noteworthy that resistance to FasL could be overcome by the use of a hexameric FasL or upon exposure of SzS cells to interferon- (IFN-) or IFN-, 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 patients with SzS and be relevant at a therapeutic level. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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