An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed Upon Deregulated BCL6 Expression

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Apr 30

PMID 25921526

Citations 50

Authors

Baochun Zhang

Dinis Pedro Calado

Zhe Wang

Sebastian Frohler

Karl Kochert

Yu Qian

Sergei B Koralov

Marc Schmidt-Supprian

Yoshiteru Sasaki

Christine Unitt

Scott Rodig

Wei Chen

Riccardo Dalla-Favera

Frederick W Alt

Laura Pasqualucci

Klaus Rajewsky

Affiliations

Soon will be listed here.

Abstract

Diffuse large B cell lymphoma (DLBCL) is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

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