Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia

The significance of DNA methyltransferase inhibition and DNA methylation for therapy response in acute myeloid leukemia

In our group we focus on epigenetic mechanisms in the pathogenesis of Acute Myeloid Leukemia. We are analyzing the effects of DNA methylation changes in AML for pathogenesis and therapy response.

For this purpose we generate leukemias with leukemogenic oncogenes in the presence or absence of transgenic DNA Methyltransferase 3B (DNMT3B).
Leukemias that arise in mice with high levels of DNMT3B expression show widespread de novo methylation of CpG islands.

  • Schenk T, Chen WC, Göllner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, Casero RA, Jr., Marton L, Woster P, Minden MD, Dugas M, Wang JC, Dick JE, Müller-Tidow C, Petrie K, Zelent A. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med. 2012;18(4):605-611. PMID:22406747

  • Agrawal-Singh S, Isken F, Agelopoulos K, Klein HU, Thoennissen NH, Koehler G, Hascher A, Bäumer N, Berdel WE, Thiede C, Ehninger G, Becker A, Schlenke P, Wang Y, McClelland M, Krug U, Koschmieder S, Büchner T, Yu DY, Singh SV, Hansen K, Serve H, Dugas M, Müller-Tidow C. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene. Blood. 2012;119(10):2346-2357. PMID:22207736

  • Carsten Müller-Tidow

    University of Münster Medical Center
    Albert-Schweitzer-Str 33
    D-48149 Münster, Germany
    Phone +49-251-835-6229/2995
    Fax +49-251-8352673