Journal article
Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene
University of Münster1
Dresden University of Technology2
University of Freiburg3
Vaccine Research Institute of San Diego4
University of California at San Diego5
Korea Research Institute of Bioscience and Biotechnology6
Risø National Laboratory for Sustainable Energy, Technical University of Denmark7
University of Copenhagen8
University of Frankfurt9
With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML.
Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML.
Functionally, PRDX2 acted as inhibitor of myeloid cell growth by reducing levels of reactive oxygen species (ROS) generated in response to cytokines. Forced PRDX2 expression inhibited c-Myc–induced leukemogenesis in vivo on BM transplantation in mice. Taken together, epigenome-wide analyses of H3Ac in AML led to the identification of PRDX2 as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML.
Language: | English |
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Publisher: | American Society of Hematology |
Year: | 2012 |
Pages: | 2346-2357 |
ISSN: | 15280020 and 00064971 |
Types: | Journal article |
DOI: | 10.1182/blood-2011-06-358705 |
ORCIDs: | 0000-0001-9657-8816 |
Acetylation Acute Disease Adolescent Adult Aged Aged, 80 and over Cell Proliferation Cells, Cultured DNA Methylation Epigenesis, Genetic Female Gene Expression Profiling Genome-Wide Association Study HL-60 Cells Histones Humans Male Middle Aged Oligonucleotide Array Sequence Analysis PRDX2 protein, human Peroxiredoxins Reactive Oxygen Species Tumor Suppressor Proteins U937 Cells Young Adult