Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice

• DOI: 10.1016/j.ccr.2005.03.037
• Publication Date: 2005-05-17T11:11:06Z
• Authors: Giorgio Cattoretti; Laura Pasqualucci; Gianna Ballon; Wayne Tam; Subhadra V. Nandula; Qiong Shen; Tongwei Mo; Vundavalli V. Murty; Riccardo Dalla-Fa...
• Keywords: 0301 basic medicine; Cancer Research; Lymphoma, B-Cell; Carcinogenesis; Plasma Cells; 610; Gene Expression; Mice, Inbred Strains; Mice, Transgenic; Mice; 03 medical and health sciences; Genetics; Animals; Humans; Animals; Cell Differentiation; Chromosome Aberrations; DNA-Binding Proteins; Disease Models; Animal; Gene Expression; Genes; Immunoglobulin; Germinal Center; Hemagglutinins; Humans; Lymphoma; B-Cell; Large B-Cell; Diffuse; Non-Hodgkin; Lymphoproliferative Disorders; Mice; Inbred C57BL; Inbred Strains; Knockout; Transgenic; Plasma Cells; Promoter Regions; Genetic; Spleen; Splenomegaly; Survival Analysis; Time Factors; Chromosome Aberrations; Mice, Knockout; B cells; Genes, Immunoglobulin; Lymphoma, Non-Hodgkin; Cell Differentiation; Cell Biology; Germinal Center; Lymphoproliferative Disorders; DNA-Binding Proteins; Mice, Inbred C57BL; Disease Models, Animal; Hemagglutinins; Oncology; FOS: Biological sciences; Lymphomas; Lymphoma, Large B-Cell, Diffuse

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 lympho- proliferative 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.