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

C04 Modelling hypomethylating therapy for monosomal cytogenetic subgroups of acute myeloid leukemia

Michael Lübbert

Michael Lübbert

Principal investigator of

DNA hypomethylating agents such as Decitabine are the first approved drugs for treatment of myelodysplastic syndromes. We recently showed that Decitabine also has remarkable activity in poor prognosis of acute myeloid leukemia (AML) with monosomal karyotype. We will investigate the mechanism of action of Decitabine in AML and will optimise the therapeutic index of Decitabine by making use of primary cell models and xenograft mouse models. Our data will improve the, until now very unfavourable, prognosis of these mostly elderly AML patients.

Selected project-relevant publications

  • Stomper J., Ihorst G., Suciu S., Sander P.N., Becker H., Wijermans P.W., Plass C., Weichenhan D., Bisse E., Claus R. and Lubbert M. (2019) Fetal hemoglobin induction during decitabine treatment of elderly patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: a potential dynamic biomarker of outcome. Haematologica 104, 59-69.
  • Blagitko-Dorfs N., Schlosser P., Greve G., Pfeifer D., Meier R., Baude A., Brocks D., Plass C. and Lubbert M. (2019) Combination treatment of acute myeloid leukemia cells with DNMT and HDAC inhibitors: predominant synergistic gene downregulation associated with gene body demethylation. Leukemia 33, 945-956.
  • Becker H., Greve G., Kataoka K., Mallm J.P., Duque-Afonso J., Ma T., Niemoller C., Pantic M., Duyster J., Cleary M.L., Schuler J., Rippe K., Ogawa S. and Lubbert M. (2019) Identification of enhancer of mRNA decapping 4 as a novel fusion partner of MLL in acute myeloid leukemia. Blood Adv 3, 761-765.
  • Flotho C., Sommer S. and Lubbert M. (2018) DNA-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia. Semin Cancer Biol 51, 68-79.
  • Blum S., Greve G. and Lubbert M. (2017) Innovative strategies for adverse karyotype acute myeloid leukemia. Curr Opin Hematol 24, 89-98.
  • Schiffmann I., Greve G., Jung M. and Lubbert M. (2016) Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives. Epigenetics 11, 858-870.
  • Morera L., Lubbert M. and Jung M. (2016) Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin Epigenetics 8, 57.
  • Lubbert M., Suciu S., Hagemeijer A., Ruter B., Platzbecker U., Giagounidis A., Selleslag D., Labar B., Germing U., Salih H.R., Muus P., Pfluger K.H., Schaefer H.E., Bogatyreva L., Aul C., De Witte T., Ganser A., Becker H., Huls G., Van Der Helm L., Vellenga E., Baron F., Marie J.P. and Wijermans P.W. (2016) Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group. Ann Hematol 95, 191-199.
  • Lubbert M. and Kuendgen A. (2015) Combining DNA methyltransferase and histone deacetylase inhibition to treat acute myeloid leukemia/myelodysplastic syndrome: achievements and challenges. Cancer 121, 498-501.
  • Greve G., Schiffmann I., Pfeifer D., Pantic M., Schuler J. and Lubbert M. (2015) The pan-HDAC inhibitor panobinostat acts as a sensitizer for erlotinib activity in EGFR-mutated and -wildtype non-small cell lung cancer cells. BMC Cancer 15, 947.
  • Greve G., Schiffmann I. and Lubbert M. (2015) Epigenetic priming of non-small cell lung cancer cell lines to the antiproliferative and differentiating effects of all-trans retinoic acid. J Cancer Res Clin Oncol 141, 2171-2180.
  • Meidhof S., Brabletz S., Lehmann W., Preca B.T., Mock K., Ruh M., Schuler J., Berthold M., Weber A., Burk U., Lubbert M., Puhr M., Culig Z., Wellner U., Keck T., Bronsert P., Kusters S., Hopt U.T., Stemmler M.P. and Brabletz T. (2015) ZEB1-associated drug resistance in cancer cells is reversed by the class I HDAC inhibitor mocetinostat. EMBO Mol Med 7, 831-847.
  • Navada S.C., Steinmann J., Lubbert M. and Silverman L.R. (2014) Clinical development of demethylating agents in hematology. J Clin Invest 124, 40-46.
  • Claus R., Pfeifer D., Almstedt M., Zucknick M., Hackanson B., Plass C. and Lubbert M. (2013) Decitabine induces very early in vivo DNA methylation changes in blasts from patients with acute myeloid leukemia. Leuk Res 37, 190-196
  • Blagitko-Dorfs N., Jiang Y., Duque-Afonso J., Hiller J., Yalcin A., Greve G., Abdelkarim M., Hackanson B. and Lubbert M. (2013) Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat. PLoS One 8, e75258.