An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression

Zhang, B.; Calado, D.P.; Wang, Z.; Froehler, S.; Koechert, K.; Qian, Y.; Koralov, S.B.; Schmidt-Supprian, M.; Sasaki, Y.; Unitt, C.; Rodig, S.; Chen, W.; Dalla-Favera, R.; Alt, F.W.; Pasqualucci, L.; Rajewsky, K.

An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression

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Item Type:	Article
Title:	An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression
Creators:	Zhang, B., Calado, D.P. ORCID: https://orcid.org/0000-0001-8239-7184, Wang, Z., Froehler, S. ORCID: https://orcid.org/0000-0001-8000-2927, Koechert, K. ORCID: https://orcid.org/0000-0002-5548-2022, Qian, Y., Koralov, S.B., Schmidt-Supprian, M., Sasaki, Y., Unitt, C., Rodig, S., Chen, W. ORCID: https://orcid.org/0000-0003-3263-1627, Dalla-Favera, R., Alt, F.W., Pasqualucci, L. and Rajewsky, K. ORCID: https://orcid.org/0000-0002-6633-6370
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-{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 ∼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.
Keywords:	B-Lymphocytes, Cell Differentiation, Cell Survival, Diffuse Large B-Cell Lymphoma, DNA-Binding Proteins, Knockout Mice, Neoplastic Gene Expression Regulation, NF-{kappa} B, Protein-Serine-Threonine Kinases, Signal Transduction, TNF Receptor-Associated Factor 3, Tumor Cell Line, Animals, Mice
Source:	Cell Reports
ISSN:	2211-1247
Publisher:	Cell Press / Elsevier
Volume:	11
Number:	5
Page Range:	715-726
Date:	5 May 2015
Official Publication:	https://doi.org/10.1016/j.celrep.2015.03.059
PubMed:	View item in PubMed

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