• Author: Agrawal-Singh, Shuchi

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Isken, Fabienne

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Agelopoulos, Konstantin

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Klein, Hans-Ulrich

    University of Muenster, Germany

  • Author: Thoennissen, Nils H.

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Koehler, Gabriele

    University of Muenster, Department of Pathology, Germany

  • Author: Hascher, Antje

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Bäumer, Nicole

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Berdel, Wolfgang E.

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Thiede, Christian

    University of Dresden, Departmenty of Medicine, Germany

  • Author: Ehninger, Gerhard

    University of Dresden, Departmenty of Medicine, Germany

  • Author: Becker, Anke

    University of Freiburg, Germany

  • Author: Schlenke, Peter

    University of Muenster, Institute of Transfusion Medicine and Transplantation Immunology, Germany

  • Author: Wang, Yipeng

    Vaccine Research Institute of San Diego, United States

  • Author: McClelland, Michael

    University of California, United States

  • Author: Krug, Utz

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Koschmieder, Steffen

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Büchner, Thomas

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Yu, Dae-Yeul

    Korea Research Institute of Bioscience and Biotechnology, Korea, Republic of

  • Author: Singh, Shailendra Vikram

    Risø National Laboratory for Sustainable Energy, Technical University of Denmark

  • Author: Hansen, Klaus

    University of Copenhagen, Denmark

  • Author: Serve, Hubert

    University of Frankfurt, Department of Medicine, Hematology, and Oncology, Germany

  • Author: Dugas, Martin

    University of Muenster, Germany

  • Author: Müller-Tidow, Carsten

    University of Muenster, Department of Medicine, Hematology, and Oncology, Germany

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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.
Original languageEnglish
JournalBlood
Publication date2012
Volume119
Issue10
Pages2346-2357
ISSN0006-4971
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 23
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