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

Sinéad T Loughran, Eva M Campion, Brendan N D'Souza, Sinéad M Smith, Katerina Vrzalikova, Kaisheng Wen, Paul G Murray, Dermot Walls

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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-kappa B 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-kappa B 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-kappa B 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-kappa B, 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.
Original languageEnglish
Pages (from-to)2787-2796
Number of pages10
JournalInternational Journal of Cancer
Issue number12
Publication statusPublished - 2011


  • apoptosis
  • Hodgkin's lymphoma
  • Bfl-1


Dive into the research topics of 'Bfl-1 is a crucial pro-survival nuclear factor-kappa B target gene in Hodgkin/Reed-Sternberg cells'. Together they form a unique fingerprint.

Cite this