Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients Academic Article Article uri icon

Overview

MeSH Major

  • Genome, Human
  • Genomics
  • Neoplasms

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.

publication date

  • September 2003

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S0145-2126(03)00018-3

PubMed ID

  • 12804643

Additional Document Info

start page

  • 841

end page

  • 51

volume

  • 27

number

  • 9