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Lymphoma

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

Leukemia volume 22, pages 835–841 (2008)Cite this article

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.

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Acknowledgements

We would like to thank J Oppatt, E Berg and H Lammert for their excellent technical assistance and Professor Dr Franco Gabrielli for providing the anti-DHRS2 (HEP27) antibody. This work was supported by a grant from the Deutsche Forschungsgemeinschaft, Klinische Forschergruppe 105.

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Authors and Affiliations

  1. Institute of Pathology, Campus Benjamin Franklin, Charité—Universitätsmedizin, Berlin, Germany

    A Ehlers, E Oker, D Lenze, H Stein & M Hummel

  2. Institute of Functional Genomics, Computational Diagnostics Group, University of Regensburg, Regensburg, Germany

    S Bentink

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  1. A Ehlers
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  2. E Oker
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  3. S Bentink
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  4. D Lenze
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  5. H Stein
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  6. M Hummel
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Correspondence to M Hummel.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Ehlers, A., Oker, E., Bentink, S. et al. Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype. Leukemia 22, 835–841 (2008). https://doi.org/10.1038/leu.2008.12

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