Document Detail

Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.
MedLine Citation:
PMID:  18256685     Owner:  NLM     Status:  MEDLINE    
A unique feature of the tumor cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA methylation, are involved in this silencing of many B-cell-associated genes. Here, we show that DNA demethylation alone or in conjunction with histone acetylation is not able to reconstitute the B-cell-gene expression program in cultured HRS cells. Instead, combined DNA demethylation and histone acetylation of B-cell lines induce an almost complete extinction of their B-cell-expression program and a tremendous upregulation of numerous Hodgkin-characteristic genes, including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the upregulation of Hodgkin-characteristic genes and the extinction of the B-cell-expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic upregulation of Hodgkin-characteristic genes thus plays--in addition to promoter DNA hypermethylation of B-cell-associated genes--a pivotal role for the reprogramming of HRS cells and explains why DNA demethylation alone is unable to reconstitute the B-cell-expression program in HRS cells.
A Ehlers; E Oker; S Bentink; D Lenze; H Stein; M Hummel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-07
Journal Detail:
Title:  Leukemia     Volume:  22     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-16     Completed Date:  2008-06-04     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  835-41     Citation Subset:  IM    
Institute of Pathology, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany.
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MeSH Terms
B-Lymphocytes / metabolism*,  pathology
Cell Transformation, Neoplastic
DNA Methylation*
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Histones / metabolism*
Hodgkin Disease / genetics,  pathology*
Reg. No./Substance:

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