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

作者：Zhang Baochun^*; Calado Dinis Pedro; Wang Zhe; Froehler Sebastian; Koechert 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

来源：Cell Reports, 2015, 11(5): 715-726.

DOI：10.1016/j.celrep.2015.03.059

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-kappa B activity, a role for oncogenic lesions that activate the alternative NF-kappa B pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-kappa B pathway, occurs in similar to 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-kappa B pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-kappa B pathway in DLBCL development.

• 出版日期2015-5-5