Inhibition of PED Protein Leads to TRAIL-Induced CLL Cell Apoptosis

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Int J Cancer. 2006 Dec 27; [Epub ahead of print]

Selective inhibition of PED protein expression sensitizes B-cell

chronic lymphocytic leukaemia cells to TRAIL-induced

apoptosis.Garofalo M, Romano G, Quintavalle C, Romano MF, Chiurazzi

F, Zanca C, Condorelli G.

Department of Cellular and Molecular Biology and Pathology,

University of Naples " Federico II, " Naples, Italy.

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.

PMID: 17192900 [PubMed - as supplied by publisher]