Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients Journal Article
| Authors: | Bäumler, C.; Duan, F.; Onel, K.; Rapaport, B.; Jhanwar, S.; Offit, K.; Elkon, K. B. |
| Article Title: | Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients |
| Abstract: | Resistance to Fas-mediated apoptosis (FMA) has been implicated in the pathogenesis of hematologic malignancies. Recently, a collaborative study showed that germline Fas mutations represent a genetic risk factor for the development of Hodgkin's and non-Hodgkin lymphoma. Here, we report that transformed B cell lines from familial lymphoma patients show a range of sensitivity to Fas-mediated apoptosis with lymphocytes from two patients with a marked resistance to Fas-, but not p53-mediated cell death. Fas resistance in these cells was associated with reduced recruitment of the initiator caspase 8 compared to cFlip, an inhibitor of apoptosis, to the death-inducing signaling complex (DISC). A decreased ratio of caspase 8 to cFlip in total cell extracts as well as in the DISC was associated with a profound disturbance of the Fas signaling cascade. We propose here that the relative reduction in caspase 8 to cFlip in the Fas DISC confers a survival advantage to lymphocytes and predisposes to the development of malignancy in some familial lymphoma patients. © 2003 Elsevier Science Ltd. All rights reserved. |
| Keywords: | signal transduction; adult; clinical article; controlled study; aged; aged, 80 and over; middle aged; unclassified drug; human cell; disease course; cancer risk; polymerase chain reaction; t-lymphocytes; cell survival; familial disease; apoptosis; fas antigen; cell line; protein; drug resistance, neoplasm; tumor cells, cultured; caspases; b lymphocyte; b cell lymphoma; blotting, western; cell transformation; intracellular signaling peptides and proteins; carrier proteins; lymphoma; tumor suppressor protein p53; fas; caspase 8; caspase 9; mitochondria; p53; receptors, tumor necrosis factor; reduction; cell extract; gamma rays; flice inhibitory protein; casp8 and fadd-like apoptosis regulating protein; antigens, cd95; membrane potentials; polymorphism, single-stranded conformational; cflip; precipitin tests; humans; human; male; female; priority journal; article; death domain receptor signaling adaptor proteins |
| Journal Title: | Leukemia Research |
| Volume: | 27 |
| Issue: | 9 |
| ISSN: | 0145-2126 |
| Publisher: | Elsevier Ltd |
| Date Published: | 2003-09-01 |
| Start Page: | 841 |
| End Page: | 851 |
| Language: | English |
| DOI: | 10.1016/s0145-2126(03)00018-3 |
| PUBMED: | 12804643 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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