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Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients.
- Source :
-
Leukemia research [Leuk Res] 2003 Sep; Vol. 27 (9), pp. 841-51. - Publication Year :
- 2003
-
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.
- Subjects :
- Aged
Aged, 80 and over
Blotting, Western
CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 8
Caspase 9
Cell Line
Death Domain Receptor Signaling Adaptor Proteins
Female
Gamma Rays adverse effects
Humans
Lymphoma pathology
Male
Membrane Potentials drug effects
Middle Aged
Mitochondria drug effects
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Precipitin Tests
Receptors, Tumor Necrosis Factor metabolism
Signal Transduction
T-Lymphocytes drug effects
T-Lymphocytes metabolism
T-Lymphocytes radiation effects
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured radiation effects
Tumor Suppressor Protein p53 metabolism
fas Receptor analysis
Apoptosis
Carrier Proteins physiology
Caspases metabolism
Drug Resistance, Neoplasm
Intracellular Signaling Peptides and Proteins
Lymphoma genetics
Lymphoma metabolism
fas Receptor physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0145-2126
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 12804643
- Full Text :
- https://doi.org/10.1016/s0145-2126(03)00018-3