Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis

Int J Cancer. 2007 Mar 15;120(6):1215-22. doi: 10.1002/ijc.22495.


B-cell chronic lymphocytic leukaemia (B-CLL) cells fail to undergo apoptosis. The mechanism underlying this resistance to cell death is still largely unknown. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells, and thus represents an attractive tool for the treatment of cancer. Unfortunately, lymphocytes from B-CLL patients are resistant to TRAIL-mediated apoptosis. Thus, we aimed to study the involvement of PED, a DED-family member with a broad antiapoptotic action, in this resistance. We demonstrate that B lymphocytes obtained from patients with B-CLL express high levels of PED. Treatment of B-CLL cells with specific PED antisense oligonucleotides, a protein synthesis inhibitor or HDAC inhibitors, induced a significant downregulation of PED and sensitized these cells to TRAIL-induced cell death. These findings suggest a direct involvement of PED in resistance to TRAIL-induced apoptosis in B-CLL. It also identifies this DED-family member as a potential therapeutic target for this form of leukaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Down-Regulation
  • Drug Resistance, Neoplasm* / genetics
  • Enzyme Inhibitors
  • Female
  • Histone Deacetylase Inhibitors
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Male
  • Oligonucleotides, Antisense / pharmacology
  • Phosphoproteins / antagonists & inhibitors*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*


  • Apoptosis Regulatory Proteins
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • PEA15 protein, human
  • Phosphoproteins
  • RNA, Messenger
  • TNF-Related Apoptosis-Inducing Ligand