Unexpected functions of nuclear factor-κB during germinal center B-cell development: implications for lymphomagenesis.

Abstract:

PURPOSE OF REVIEW:B-cell tumors originating from the transformation of germinal center B cells frequently harbor genetic mutations, leading to constitutive activation of the nuclear factor-κB (NF-κB) signaling pathway. The present review highlights recent insights into the roles of separate NF-κB transcription factors in germinal center B-cell development and discusses implications of the results for germinal center lymphomagenesis. RECENT FINDINGS:Understanding how aberrant NF-κB activation promotes tumorigenesis requires the understanding of the role of NF-κB in the tumor-precursor cells. Despite extensive knowledge on NF-κB biology, the function of this complex signaling pathway in the differentiation of germinal center B cells is largely unknown. The present review will discuss recent findings that revealed distinct roles of separate NF-κB transcription factors during the germinal center reaction in the context of germinal center lymphomagenesis. Most notably, a single NF-κB subunit, c-REL, was found to be required for the maintenance of the germinal center reaction and was associated with the activation of a metabolic program that promotes cell growth. SUMMARY:Identifying the biological roles of the separate NF-κB transcription factor subunits in germinal center biology will help to better understand the pathogenic consequences of their constitutive activation in B-cell tumors. This knowledge may be exploited for the development of targeted antitumor therapies aimed at inhibiting selectively those components of aberrant NF-κB activity which contribute to pathogenesis.

journal_name

Curr Opin Hematol

authors

Klein U,Heise N

doi

10.1097/MOH.0000000000000160

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

379-87

issue

4

eissn

1065-6251

issn

1531-7048

pii

00062752-201507000-00016

journal_volume

22

pub_type

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