XIAP-mediated caspase inhibition in Hodgkin's lymphoma-derived B cells

J Exp Med. 2003 Jul 21;198(2):341-7. doi: 10.1084/jem.20021279.


The malignant Hodgkin and Reed-Sternberg cells of Hodgkin's lymphoma (HL) and HL-derived B cell lines were previously shown to be resistant to different apoptotic stimuli. We show here that cytochrome c fails to stimulate caspases-9 and -3 activation in cytosolic extracts of HL-derived B cells, which is due to high level expression of X-linked inhibitor of apoptosis (XIAP). Coimmunoprecipitation studies revealed that XIAP, apoptosis protease-activating factor-1, and caspase-3 are complexed in HL-derived B cell lysates. Even after stimulation with exogenous cytochrome c and dATP, XIAP impairs the proteolytic processing and activation of caspase-3. In cytosolic extracts, inhibition of XIAP by the second mitochondria-derived activator of caspases (Smac)/DIABLO, or immunodepletion of XIAP restores cytochrome c-triggered processing and activation of caspase-3. Smac or a Smac-derived agonistic peptide also sensitized intact HL-derived B cells for the apoptotic action of staurosporine. Finally, Hodgkin and Reed-Sternberg cells of primary tumor HL tissues also constitutively and abundantly express XIAP. The results of this paper suggest that high level XIAP expression is a hallmark of HL, which may play a crucial role in resistance to apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Caspase Inhibitors*
  • Cytochrome c Group / metabolism
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / pathology
  • Humans
  • Proteins / immunology*
  • Reed-Sternberg Cells / immunology*
  • Tumor Cells, Cultured
  • X-Linked Inhibitor of Apoptosis Protein


  • Caspase Inhibitors
  • Cytochrome c Group
  • Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human