Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice.
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.
Cattoretti
Giorgio
G
Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA.
Pasqualucci
Laura
L
Ballon
Gianna
G
Tam
Wayne
W
Nandula
Subhadra V
SV
Shen
Qiong
Q
Mo
Tongwei
T
Murty
Vundavalli V
VV
Dalla-Favera
Riccardo
R
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics; D018858:Germinal Center / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006388:Hemagglutinins / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D013154:Spleen / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors
C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D006388:Hemagglutinins; D051560:Proto-Oncogene Proteins c-bcl-6