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Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma

Item Type:Article
Title:Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma
Creators Name:Calado, D.P. and Zhang, B. and Srinivasan, L. and Sasaki, Y. and Seagal, J. and Unitt, C. and Rodig, S. and Kutok, J. and Tarakhovsky, A. and Schmidt-Supprian, M. and Rajewsky, K.
Abstract:Diffuse large B cell lymphoma (DLBCL) comprises disease entities with distinct genetic profiles, including germinal center B cell (GCB)-like and activated B cell (ABC)-like DLBCLs. Major differences between these two subtypes include genetic aberrations leading to constitutive NF-κB activation and interference with terminal B cell differentiation through BLIMP1 inactivation, observed in ABC- but not GCB-DLBCL. Using conditional gain-of-function and/or loss-of-function mutagenesis in the mouse, we show that constitutive activation of the canonical NF-κB pathway cooperates with disruption of BLIMP1 in the development of a lymphoma that resembles human ABC-DLBCL. Our work suggests that both NF-κB signaling, as an oncogenic event, and BLIMP1, as a tumor suppressor, play causal roles in the pathogenesis of ABC-DLBCL.
Keywords:Cell Proliferation, Diffuse Large B-Cell Lymphoma, Germinal Center, IκB Kinase, Mutation, NF-κB, Plasma Cells, Transcription Factors, Animals, Mice
Source:Cancer Cell
ISSN:1535-6108
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:18
Number:6
Page Range:580-589
Date:14 December 2010
Official Publication:https://doi.org/10.1016/j.ccr.2010.11.024
PubMed:View item in PubMed

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