SEARCH:   Advanced

Blood, 15 March 2006, Vol. 107, No. 6, pp. 2493-2500. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-09-3765. This Article Full Text (PDF) All Versions of this Article: 2005-09-3765v1 107/6/2493    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 Ushmorov, A. Articles by Wirth, T. Search for Related Content PubMed PubMed Citation Articles by Ushmorov, A. Articles by Wirth, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 21, 2005 Accepted October 28, 2005 Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma Alexey Ushmorov, Frank Leithauser, Olena Sakk, Andreas Weinhausel, Sergey W Popov, Peter Moller, and Thomas Wirth* Department of Physiological Chemistry, University of Ulm, Ulm, Germany Department of Pathology, University of Ulm, Ulm, Germany Division of Molecular Diagnostics, ARC Seibersdorf Research GmbH, Seibersdorf, Austria * Corresponding author; email: thomas.wirth{at}uni-ulm.de. Many B-lineage-specific genes are down-regulated in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We investigated the involvement of epigenetic modifications in gene silencing in cHL cell lines and in microdissected primary HRS cells. We assessed the expression and methylation status of CD19, CD20, CD79b, SYK, PU.1, BOB.1/OBF.1, BCMA, and LCK, all of which are typically down-regulated in cHL. We could reactivate gene expression in cHL cell lines with the DNA demethylating agent 5-aza-deoxycytidine (5-aza-dC). Using methylation specific PCR (MSP), bisulfite genomic sequencing and digestion with methylation-sensitive endonuclease followed by PCR we determined the methylation status of promoter regions of PU.1, BOB.1/OBF.1, CD19 and SYK and CD79b. Down-regulation of transcription typically correlated with hypermethylation. Using bisulfite genomic sequencing we found that in microdissected HRS cells of primary cHL SYK, BOB.1/OBF.1, and CD79b promoters were also hypermethylated. Ectopic expression of both Oct2 and PU.1 in a cHL cell line potentiated endogenous PU.1 and SYK expression after 5-aza-dC treatment. These observations indicate that silencing of the B-cell-specific genes in cHL may be the consequence of a compromised regulatory network, were down-regulation of a few master transcription factors results in silencing of numerous genes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Classical Hodgkin lymphoma: an epigenetically determined disease? Juan F. García Blood 2006 107: 2217-2218. [Full Text] [PDF] This article has been cited by other articles: R. D. Gascoyne Stem cells in Hodgkin lymphoma? Blood, June 4, 2009; 113(23): 5694 - 5694. [Full Text] [PDF] R. J. Jones, C. D. Gocke, Y. L. Kasamon, C. B. Miller, B. Perkins, J. P. Barber, M. S. Vala, J. M. Gerber, L. L. Gellert, M. Siedner, et al. Circulating clonotypic B cells in classic Hodgkin lymphoma Blood, June 4, 2009; 113(23): 5920 - 5926. [Abstract] [Full Text] [PDF] S. Garaud, C. Le Dantec, S. Jousse-Joulin, C. Hanrotel-Saliou, A. Saraux, R. A. Mageed, P. Youinou, and Y. Renaudineau IL-6 Modulates CD5 Expression in B Cells from Patients with Lupus by Regulating DNA Methylation J. Immunol., May 1, 2009; 182(9): 5623 - 5632. [Abstract] [Full Text] [PDF] A. Mankai, A. Bordron, Y. Renaudineau, C. Martins-Carvalho, S. Takahashi, I. Ghedira, C. Berthou, and P. Youinou Purine-Rich Box-1-Mediated Reduced Expression of CD20 Alters Rituximab-Induced Lysis of Chronic Lymphocytic Leukemia B Cells Cancer Res., September 15, 2008; 68(18): 7512 - 7519. [Abstract] [Full Text] [PDF] D. Buglio, G. V. Georgakis, S. Hanabuchi, K. Arima, N. M. Khaskhely, Y.-J. Liu, and A. Younes Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines Blood, August 15, 2008; 112(4): 1424 - 1433. [Abstract] [Full Text] [PDF] C. F. Skibola, J. D. Curry, and A. Nieters Genetic susceptibility to lymphoma Haematologica, July 1, 2007; 92(7): 960 - 969. [Abstract] [Full Text] [PDF] Y. Natkunam, E. D. Hsi, P. Aoun, S. Zhao, P. Elson, B. Pohlman, H. Naushad, M. Bast, R. Levy, and I. S. Lossos Expression of the human germinal center-associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival Blood, January 1, 2007; 109(1): 298 - 305. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020