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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1475-1484. Prepublished online as a Blood First Edition Paper on October 23, 2003October 16, 2003; DOI 10.1182/blood-2003-06-2116. This Article Full Text (PDF) All Versions of this Article: 2003-06-2116v1 2003-06-2116v2 103/4/1475    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Greenwald, R. J Articles by Denis, G. V Search for Related Content PubMed PubMed Citation Articles by Greenwald, R. J Articles by Denis, G. V Social Bookmarking                   What's this? Submitted June 26, 2003 Accepted October 8, 2003 Eµ-BRD2 transgenic mice develop B-cell lymphoma and leukemia Rebecca J Greenwald, Joseph R Tumang, Anupama Sinha, Nicolas Currier, Robert D Cardiff, Thomas L Rothstein, Douglas V Faller, and Gerald V Denis* Department of Pathology, Immunology Research Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Immunobiology Unit, Departments of Medicine and Microbiology, Evans Biomedical Research Center, Boston Medical Center, Boston, MA, USA Cancer Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA Center for Comparative Medicine, University of California, Davis, CA, USA * Corresponding author; email: gdenis{at}bu.edu. Transgenic mice with lymphoid-restricted overexpression of the double bromodomain protein Brd2 develop splenic B cell lymphoma and, upon transplantation, B-cell leukemia with leukemic infiltrates in liver and lung. Brd2 is a nuclear-localized transcription factor kinase that is most closely related to TAFII250 and the Drosophila homeotic factor female sterile homeotic. Constitutive overexpression of BRD2 in the lymphoid compartment increases cyclin A transcription, 'priming' transgenic B cells for proliferation. Mice stochastically develop an aggressive B-cell lymphoma with the features of B-1 cells, including CD5 and surface IgM expression. The B-cell lymphoma is monoclonal for immunoglobulin gene rearrangement and is phenotypically stable. The lymphoblasts are very large and express a transcriptome that is similar to some human non-Hodgkin lymphomas. Both a wild type BRD2 transgene and a kinase-null point mutant drive lymphomagenesis; therefore we propose that, rather than kinase activity, Brd2-mediated recruitment of E2Fs and a specific histone acetyltransferase to the cyclin A promoter in both types of transgenic mice is a mechanistic basis for neoplasia. This report is the first to describe a transgenic mouse model for constitutive expression of a protein with more than one bromodomain. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Kaku and T. L. Rothstein Fas Apoptosis Inhibitory Molecule Expression in B Cells Is Regulated through IRF4 in a Feed-Forward Mechanism J. Immunol., November 1, 2009; 183(9): 5575 - 5581. [Abstract] [Full Text] [PDF] P. B. Romesser, D. H. Perlman, D. V. Faller, C. E. Costello, M. E. McComb, and G. V. Denis Development of a Malignancy-Associated Proteomic Signature for Diffuse Large B-Cell Lymphoma Am. J. Pathol., July 1, 2009; 175(1): 25 - 35. [Abstract] [Full Text] [PDF] M. Ottinger, D. Pliquet, T. Christalla, R. Frank, J. P. Stewart, and T. F. Schulz The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters J. Virol., May 1, 2009; 83(9): 4423 - 4434. [Abstract] [Full Text] [PDF] M. E. Lenburg, A. Sinha, D. V. Faller, and G. V. Denis Tumor-specific and Proliferation-specific Gene Expression Typifies Murine Transgenic B Cell Lymphomagenesis J. Biol. Chem., February 16, 2007; 282(7): 4803 - 4811. [Abstract] [Full Text] [PDF] M. Ottinger, T. Christalla, K. Nathan, M. M. Brinkmann, A. Viejo-Borbolla, and T. F. Schulz Kaposi's Sarcoma-Associated Herpesvirus LANA-1 Interacts with the Short Variant of BRD4 and Releases Cells from a BRD4- and BRD2/RING3-Induced G1 Cell Cycle Arrest J. Virol., November 1, 2006; 80(21): 10772 - 10786. [Abstract] [Full Text] [PDF] H. Longe, D. V. Faller, and G. V. Denis Telomere-Based Pre-Clinical Therapy in a Murine Model of Non-Hodgkin's Lymphoma of the Diffuse Large B Cell (DLCL)Type. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 607 - 607. [Abstract] U. Modlich, O. S. Kustikova, M. Schmidt, C. Rudolph, J. Meyer, Z. Li, K. Kamino, N. von Neuhoff, B. Schlegelberger, K. Kuehlcke, et al. Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis Blood, June 1, 2005; 105(11): 4235 - 4246. [Abstract] [Full Text] [PDF]

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