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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5536-5548. Prepublished online as a Blood First Edition Paper on March 23, 2009; DOI 10.1182/blood-2008-12-193037. This Article Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-12-193037v1 113/22/5536    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ci, W. Articles by Melnick, A. Search for Related Content PubMed PubMed Citation Articles by Ci, W. Articles by Melnick, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 30, 2008 Accepted March 17, 2009 The BCL6 transcriptional program features repression of multiple oncogenes in primary B-cells and is deregulated in DLBCL Weimin Ci, Jose M. Polo, Leandro Cerchietti, Rita Shaknovich, Ling Wang, Shao Ning Yang, Kenny Ye, Pedro Farinha, Douglas E. Horsman, Randy D. Gascoyne, Olivier Elemento*, and Ari Melnick Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, United States Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States Department of Public Health, Division of Biostatistics, Albert Einstein College of Medicine, Bronx, NY, United States Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, United States * Corresponding author; email: ole2001{at}med.cornell.edu. The BCL6 transcriptional repressor is required for development of germinal center (GC) B-cells and when expressed constitutively causes diffuse large B-cell lymphomas (DLBCLs). We examined genome-wide BCL6 promoter binding in GC B-cells vs. DLBCLs to better understand its function in these settings. BCL6 bound to both distinct and common sets of functionally related gene in normal GC cells vs. DLBCL cells. Certain BCL6 target genes were preferentially repressed in GC B-cells, but not DLBCL cells. Several such genes have prominent oncogenic functions, such as BCL2, MYC, BMI1, EIF4E, JUNB and CCND1. BCL6 and BCL2 expression was negatively correlated in primary DLBCLs except in the presence of BCL2 translocations. The specific BCL6 inhibitor RI-BPI induced expression of BCL2 and other oncogenes, consistent with direct repression effects by BCL6. These data are consistent with a model whereby BCL6 can directly silence oncogenes in GC B-cells and counterbalance its own tumorigenic potential. Finally, a BCL6 consensus sequence and binding sites for other physiologically relevant transcription factors were highly enriched among target genes, and distributed in a pathway-dependent manner, suggesting that BCL6 forms specific regulatory circuits with other B-cell transcriptional factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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