Deregulated BCL6 Expression Recapitulates the Pathogenesis of Human Diffuse Large B Cell Lymphomas in Mice

Cancer Cell. 2005 May;7(5):445-55. doi: 10.1016/j.ccr.2005.03.037.

Abstract

Diffuse large B cell lymphomas (DLBCL) derive from germinal center (GC) B cells and display chromosomal alterations deregulating the expression of BCL6, a transcriptional repressor required for GC formation. To investigate the role of BCL6 in DLBCL pathogenesis, we have engineered mice that express BCL6 constitutively in B cells by mimicking a chromosomal translocation found in human DLBCL. These mice display increased GC formation and perturbed post-GC differentiation characterized by a decreased number of post-isotype switch plasma cells. Subsequently, these mice develop a lymphoproliferative syndrome that culminates with the development of lymphomas displaying features typical of human DLBCL. These results define the oncogenic role of BCL6 in the pathogenesis of DLBCL and provide a faithful mouse model of this common disease.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Chromosome Aberrations
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal*
  • Gene Expression / genetics*
  • Genes, Immunoglobulin / genetics
  • Germinal Center / chemistry
  • Germinal Center / metabolism
  • Germinal Center / pathology
  • Hemagglutinins / genetics
  • Humans
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology*
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Lymphoma, Non-Hodgkin / genetics
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Plasma Cells / chemistry
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-bcl-6
  • Spleen / chemistry
  • Spleen / metabolism
  • Spleen / pathology
  • Splenomegaly / pathology
  • Survival Analysis
  • Time Factors

Substances

  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Hemagglutinins
  • Proto-Oncogene Proteins c-bcl-6