Mechanisms and consequences of constitutive NF-κB activation in B-cell lymphoid malignancies.

Abstract:

:The discovery of constitutive nuclear factor-κB (NF-κB) activation in Hodgkin's lymphoma tumor cells almost two decades ago was one of the first reports that directly connected deregulated NF-κB signaling to human cancer. Subsequent studies demonstrated that enhanced NF-κB signaling is a common hallmark of many lymphoid malignancies, including Hodgkin lymphoma, mucosa-associated lymphoid tissue lymphoma, diffuse large B-cell lymphoma and multiple myeloma. By inducing an anti-apoptotic and pro-proliferative gene program, NF-κB is involved in lymphoma survival and growth. Identification of somatic mutations that led to activation of oncogenes and inactivation of tumor suppressor genes in the pathway revealed that specific pathogenic mechanisms are responsible for constitutive NF-κB activation in different lymphoma entities. Thus, the identification of distinct oncogenic events is reflecting the diverse cellular origins of the different lymphomas. Further, elucidation of the mechanisms that drive NF-κB in lymphoma is of high clinical relevance as it will allow the design of target-directed precision therapy. Indeed, a number of drugs that impair constitutive NF-κB activation in lymphoid malignancies are currently in preclinical or clinical development.

journal_name

Oncogene

journal_title

Oncogene

authors

Nagel D,Vincendeau M,Eitelhuber AC,Krappmann D

doi

10.1038/onc.2013.565

subject

Has Abstract

pub_date

2014-12-11 00:00:00

pages

5655-65

issue

50

eissn

0950-9232

issn

1476-5594

pii

onc2013565

journal_volume

33

pub_type

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