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

Leukemia. 2008 Apr;22(4):835-41. doi: 10.1038/leu.2008.12. Epub 2008 Feb 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Cell Transformation, Neoplastic
  • DNA Methylation*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism*
  • Hodgkin Disease / genetics
  • Hodgkin Disease / pathology*
  • Phenotype

Substances

  • Histones