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An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression
journal contributionposted on 2020-09-23, 12:07 authored by 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
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.
AnimalsB-LymphocytesCell DifferentiationCell Line, TumorCell SurvivalDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansLymphoma, Large B-Cell, DiffuseMiceMice, KnockoutNF-kappa BProtein-Serine-Threonine KinasesProto-Oncogene Proteins c-bcl-6Signal TransductionTNF Receptor-Associated Factor 3Calado0601 Biochemistry and Cell Biology