Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype

Ehlers, A. and Oker, E. and Bentink, S. and Lenze, D. and Stein, H. and Hummel, M. (2008) Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype. LEUKEMIA, 22 (4). pp. 835-841. ISSN 0887-6924,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: REED-STERNBERG CELLS; GENE-EXPRESSION; IMMUNOGLOBULIN TRANSCRIPTION; FOLLICULAR LYMPHOMA; DISEASE; IDENTIFICATION; REARRANGEMENTS; INHIBITION; REPRESENT; PATTERN; methylation; acetylation; classical Hodgkin lymphoma; epigenetic
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Nov 2020 08:29
Last Modified: 05 Nov 2020 08:30
URI: https://pred.uni-regensburg.de/id/eprint/31132

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