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

Cancer Cell. 2010 Dec 14;18(6):580-9. doi: 10.1016/j.ccr.2010.11.024.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Germinal Center / physiology
  • I-kappa B Kinase / genetics
  • Lymphoma, Large B-Cell, Diffuse / etiology*
  • Mice
  • Mutation
  • NF-kappa B / metabolism*
  • Plasma Cells / physiology
  • Positive Regulatory Domain I-Binding Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • NF-kappa B
  • Prdm1 protein, mouse
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1
  • I-kappa B Kinase
  • Ikbkb protein, mouse