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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4166-4178. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-04-1018. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2003-04-1018v1 102/12/4166    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Portis, T. Articles by Longnecker, R. Search for Related Content PubMed PubMed Citation Articles by Portis, T. Articles by Longnecker, R. Related Collections Gene Expression Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Epstein-Barr Virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma Toni Portis, Patricia Dyck, and Richard Longnecker From the Department of Microbiology and Immunology and the Department of Computer Science and Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Epstein-Barr virus (EBV) is associated with the development of a variety of malignancies, including Hodgkin lymphoma. One of the few viral transcripts expressed in EBV-positive Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma is latent membrane protein 2A (LMP2A). This viral protein blocks B-cell receptor (BCR)-signaling in vitro. Furthermore, expression of LMP2A in developing B cells in vivo induces a global down-regulation of genes necessary for proper B-cell development. In this study we have analyzed gene transcription in primary B cells from LMP2A transgenic mice, LMP2A-expressing human B-cell lines, and LMP2A-positive and -negative EBV-infected lymphoblastoid cell lines (LCLs). We demonstrate that LMP2A increases the expression of genes associated with cell cycle induction and inhibition of apoptosis, alters the expression of genes involved in DNA and RNA metabolism, and decreases the expression of B-cell-specific factors and genes associated with immunity. Furthermore, many alterations in gene expression induced by LMP2A are similar to those recently described in HRS cells of Hodgkin lymphoma and activated, proliferating germinal center centroblasts/centrocytes. These correlations suggest that LMP2A expression in EBV-infected B cells may lead to the induction and maintenance of an activated, proliferative state that could ultimately result in the development of Hodgkin lymphoma. (Blood. 2003;102: 4166-4178) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. J. Anderson and R. Longnecker EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway J. Gen. Virol., July 1, 2008; 89(7): 1563 - 1568. [Abstract] [Full Text] [PDF] G Kapatai and P Murray Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma J. Clin. Pathol., December 1, 2007; 60(12): 1342 - 1349. [Abstract] [Full Text] [PDF] M. Fukuda and R. Longnecker Epstein-Barr Virus Latent Membrane Protein 2A Mediates Transformation through Constitutive Activation of the Ras/PI3-K/Akt Pathway J. Virol., September 1, 2007; 81(17): 9299 - 9306. [Abstract] [Full Text] [PDF] R. F. Ambinder Epstein-Barr Virus and Hodgkin Lymphoma Hematology, January 1, 2007; 2007(1): 204 - 209. [Abstract] [Full Text] [PDF] M. Swanson-Mungerson, R. Bultema, and R. Longnecker Epstein-Barr Virus LMP2A Enhances B-Cell Responses In Vivo and In Vitro J. Virol., July 15, 2006; 80(14): 6764 - 6770. [Abstract] [Full Text] [PDF] M. M. Brinkmann and T. F. Schulz Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1047 - 1074. [Abstract] [Full Text] [PDF] D. M. Pegtel, A. Subramanian, T.-S. Sheen, C.-H. Tsai, T. R. Golub, and D. A. Thorley-Lawson Epstein-Barr-Virus-Encoded LMP2A Induces Primary Epithelial Cell Migration and Invasion: Possible Role in Nasopharyngeal Carcinoma Metastasis J. Virol., December 15, 2005; 79(24): 15430 - 15442. [Abstract] [Full Text] [PDF] C. A. Moody, R. S. Scott, N. Amirghahari, C.-A. Nathan, L. S. Young, C. W. Dawson, and J. W. Sixbey Modulation of the Cell Growth Regulator mTOR by Epstein-Barr Virus-Encoded LMP2A J. Virol., May 1, 2005; 79(9): 5499 - 5506. [Abstract] [Full Text] [PDF] S. Poppema Immunobiology and Pathophysiology of Hodgkin Lymphomas Hematology, January 1, 2005; 2005(1): 231 - 238. [Abstract] [Full Text] [PDF] S. Stewart, C. W. Dawson, K. Takada, J. Curnow, C. A. Moody, J. W. Sixbey, and L. S. Young Epstein-Barr virus-encoded LMP2A regulates viral and cellular gene expression by modulation of the NF-{kappa}B transcription factor pathway PNAS, November 2, 2004; 101(44): 15730 - 15735. [Abstract] [Full Text] [PDF] J. A. Morrison, M. L. Gulley, R. Pathmanathan, and N. Raab-Traub Differential Signaling Pathways Are Activated in the Epstein-Barr Virus-Associated Malignancies Nasopharyngeal Carcinoma and Hodgkin Lymphoma Cancer Res., August 1, 2004; 64(15): 5251 - 5260. [Abstract] [Full Text] [PDF] R. M. Meyer, R. F. Ambinder, and S. 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