Bfl-1 is a crucial pro-survival nuclear factor-κB target gene in Hodgkin/Reed-Sternberg cells

✍ Scribed by Sinéad T. Loughran; Eva M. Campion; Brendan N. D'Souza; Sinéad M. Smith; Katerina Vrzalikova; Kaisheng Wen; Paul G. Murray; Dermot Walls

• Book ID: 102864289
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 811 KB
• Volume: 129
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.25950

✦ Synopsis

Abstract

Hodgkin/Reed‐Sternberg (H/RS) cells are believed to represent clonal progeny of Germinal Centre B cells that have escaped negative selection by evading apoptosis. Aberrant constitutive activity of the transcription factor NF‐κB plays a key role in the pathogenesis of Hodgkin's Lymphoma (HL), conferring a survival advantage on H/RS cells. Bfl‐1 is a pro‐survival NF‐κB target gene from the Bcl‐2 family of apoptosis‐regulating proteins. Here, we report that bfl‐1 (also known as A1 or GRS) is frequently expressed in primary H/RS cells from HL tumor biopsies and that elevated bfl‐1 expression is a feature of H/RS derived cell lines. We show that bfl‐1 is an NF‐κB target gene in this cell context and that this regulation is effected through a p65‐binding DNA element located in its promoter. We demonstrate that ectopic Bfl‐1 can rescue cultured H/RS cells from apoptosis induced by pharmacological inhibitors of NF‐κB, and that knockdown of bfl‐1 potentiates the pro‐apoptotic effect of these agents. These findings are the first indication that Bfl‐1 plays a crucial role in setting the elevated threshold of resistance of this malignant cell type to apoptosis.