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

Baochun Zhang, Dinis Pedro Calado, Zhe Wang, Sebastian Fröhler, Karl Köchert, 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

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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 coexistswith BCL6 translocation, which prevents terminalBcell differentiation. Accordingly, in a mouse modelconstitutive 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.

Original languageEnglish
Pages (from-to)715-726
Number of pages12
JournalCell Reports
Volume11
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

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