Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis
✍ Scribed by Michela Garofalo; Giulia Romano; Cristina Quintavalle; Maria Fiammetta Romano; Federico Chiurazzi; Ciro Zanca; Gerolama Condorelli
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- French
- Weight
- 489 KB
- Volume
- 120
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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.