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  • Z01
    • Backofen
    • Manke
  • Z02
    • Breit
    • Einsle
    • Günther
  • Z03 Central tasks

C05 Functional role of epigenetic changes in juvenile myelomonocytic leukaemia-initiating cells

Christian Flotho

Christian Flotho

Principal investigator of

Juvenile myelomonocytic leukaemia (JMML) is a malignant myeloproliferative disorder of early childhood. We established a xenotransplantation model of JMML and investigated the stability of epigenetic profiles in JMML-initiating cells. We will focus on the functional role of epigenetics for the leukaemia-initiating activity of JMML cells. We will use clinical samples of JMML patients before and after treatment with DNA methyltransferase inhibitors (DNMTi) to investigate the clonal architecture and intra-patient diversity in JMML and to integrate genome-wide DNA methylation profiles and alterations in the proteome.

Selected project-relevant publications

  • Wilhelm T., Lipka D.B., Witte T., Wierzbinska J.A., Fluhr S., Helf M., Mucke O., Claus R., Konermann C., Nollke P., Niemeyer C.M., Flotho C. and Plass C. (2016) Epigenetic silencing of AKAP12 in juvenile myelomonocytic leukemia. Epigenetics 11, 110-119.
  • Krombholz C.F., Aumann K., Kollek M., Bertele D., Fluhr S., Kunze M., Niemeyer C.M., Flotho C. and Erlacher M. (2016) Long-term serial xenotransplantation of juvenile myelomonocytic leukemia recapitulates human disease in Rag2-/-gammac-/- mice. Haematologica 101, 597-606.
  • Fluhr S., Boerries M., Busch H., Symeonidi A., Witte T., Lipka D.B., Mucke O., Nollke P., Krombholz C.F., Niemeyer C.M., Plass C. and Flotho C. (2016) CREBBP is a target of epigenetic, but not genetic, modification in juvenile myelomonocytic leukemia. Clin Epigenetics 8, 50.
  • Cseh A.M., Niemeyer C.M., Yoshimi A., Catala A., Fruhwald M.C., Hasle H., Van Den Heuvel-Eibrink M.M., Lauten M., De Moerloose B., Smith O.P., Bernig T., Gruhn B., Kulozik A.E., Metzler M., Olcay L., Suttorp M., Furlan I., Strahm B. and Flotho C. (2016) Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group. Br J Haematol 172, 930-936.
  • Cseh A., Niemeyer C.M., Yoshimi A., Dworzak M., Hasle H., Van Den Heuvel-Eibrink M.M., Locatelli F., Masetti R., Schmugge M., Gross-Wieltsch U., Candas A., Kulozik A.E., Olcay L., Suttorp M., Furlan I., Strahm B. and Flotho C. (2015) Bridging to transplant with azacitidine in juvenile myelomonocytic leukemia: a retrospective analysis of the EWOG-MDS study group. Blood 125, 2311-2313.
  • Poetsch A.R., Lipka D.B., Witte T., Claus R., Nollke P., Zucknick M., Olk-Batz C., Fluhr S., Dworzak M., De Moerloose B., Stary J., Zecca M., Hasle H., Schmugge M., Van Den Heuvel-Eibrink M.M., Locatelli F., Niemeyer C.M., Flotho C. and Plass C. (2014) RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia. Epigenetics 9, 1252-1260.