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Selective inhibition of PED protein expression sensitizes B‐cell chronic lymphocytic leukaemia cells to TRAIL‐induced apoptosis
Author(s) -
Garofalo Michela,
Romano Giulia,
Quintavalle Cristina,
Romano Maria Fiammetta,
Chiurazzi Federico,
Zanca Ciro,
Condorelli Gerolama
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22495
Subject(s) - apoptosis , cancer research , chronic lymphocytic leukemia , programmed cell death , downregulation and upregulation , immunology , biology , medicine , leukemia , gene , genetics
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. © 2006 Wiley‐Liss, Inc.