An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expressionMore about Open Access at the Crick
Authors listBaochun Zhang Dinis 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.
Journal Cell Reports
Issue number 5