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 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 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 Ushmorov, A. Articles by Wirth, T. Search for Related Content PubMed PubMed Citation Articles by Ushmorov, A. Articles by Wirth, T. Related Collections Gene Expression Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma Alexey Ushmorov, Frank Leithäuser, Olena Sakk, Andreas Weinhaüsel, Sergey W. Popov, Peter Möller, and Thomas Wirth From the Departments of Physiological Chemistry and Pathology, University of Ulm, Germany; and the Division of Molecular Diagnostics, ARC Seibersdorf Research, Seibersdorf, Austria. 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 polymerase chain reaction (MSP), bisulfite genomic sequencing, and digestion with methylation-sensitive endonuclease followed by polymerase chain reaction (PCR), we determined the methylation status of promoter regions of PU.1, BOB.1/OBF.1, CD19, 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 where down-regulation of a few master transcription factors results in silencing of numerous genes. (Blood. 2006;107:2493-2500) 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: 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]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020