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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Epigenetic down-regulation of the tumor suppressor gene PRDM1/Blimp-1 in diffuse large B cell lymphomas: A potential role of the microRNA let-7
American Journal of Pathology, Volume 177, No. 3, Year 2010
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Description
PRDM1/Blimp-1, a master regulator for B cell terminal differentiation, is a putative tumor suppressor in diffuse large B cell lymphomas (DLBCL). Inactivating mutations of PRDM1 have been previously identified in a subset of nongerminal center B cell - like (GCB) DLBCL. We investigated the presence of alternative mechanisms of down-regulating PRDM1 in a cohort of 25 primary DLBCL and six DLBCL cell lines. While some DLBCL, predominantly the GCB-type, showed low levels of both PRDM1 α mRNA and protein, presumably as a result of direct transcription repression, discordant expressions between the two were identified in a subset of DLBCL without PRDM1 mutations, the primarily non-GCB type, consistent with translational down-regulation. This subset of DLBCL exhibits relatively high PRDM1 α mRNA levels but low levels of PRDM1. Data obtained from expression analysis, luciferase reporter assays, and transfection experiments support a role of targeting of PRDM1 by microRNA let-7 family in mediating this down-regulation. Let-7 , in particular let-7b , is overexpressed in DLBCL relative to normal GCB cells , suggesting that it is deregulated. Thus, abnormal epigenetic down-regulation of PRDM1 by let-7 and other microRNAs may represent an alternative mechanism of reducing normal PRDM1 function in a subset of DLBCL with relatively high PRDM1 α mRNA expression and unmutated PRDM1. These findings provide further evidence for an important role of impairment of terminal B cell differentiation in DLBCL pathogenesis. Copyright © American Society for Investigative Pathology.
Authors & Co-Authors
Nie, Kui
United States, New York
Weill Cornell Medicine
Zhang, Taotao
United States, New York
Weill Cornell Medicine
Allawi, Hatim
United States, Madison
Third Wave Technologies, Inc.
Jordan, Amman
King Hussein Institute for Biotechnology and Cancer
Gomez, Mario
United States, New York
Weill Cornell Medicine
United States, Old Westbury
New York Institute of Technology College of Osteopathic Medicine
Liu, Yifang
United States, New York
Weill Cornell Medicine
Chadburn, Amy
United States, New York
Weill Cornell Medicine
United States, Chicago
Northwestern University Feinberg School of Medicine
Wang, Y. Lynn
United States, New York
Weill Cornell Medicine
Knowles, Daniel M.
United States, New York
Weill Cornell Medicine
Tam, Wayne
United States, New York
Weill Cornell Medicine
Statistics
Citations: 66
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.2353/ajpath.2010.091291
e-ISSN:
15252191
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study