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

Zhang, Baochun  ,  Calado, DinisPedro  ,  Wang, Zhe  ,  Fröhler, Sebastian  ,  Köchert, Karl  ,  Qian, Yu  ,  Koralov, Sergei B.  ,  Schmidt-Supprian, Marc  ,  Sasaki, Yoshiteru  ,  Unitt, Christine  ,  Rodig, Scott  ,  Chen, Wei  ,  Dalla-Favera, Riccardo  ,  Alt, Frederick W.  ,  Pasqualucci, Laura  ,  Rajewsky, Klaus

11 ( 5 )  , pp.715 - 726 , 2015-05-05 , Elsevier
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.

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