Epigenetic Regulation of normal hematopoiesis and its dysregulation in myeloid neoplasia

Comparative characterization of azacytidine-induced RNA and DNA demethylation in myeloid leukemia

Myeloid leukemias represent one of the major models for the field of cancer epigenetics. This is exemplified by the fact that Myelodysplastic Syndrome and Acute Myeloid Leukemia represent the primary indications for the clinical use of the DNA methyltransferase inhibitors azacytidine and decitabine.
In previous studies, we have characterized drug-induced demethylation in myeloid leukemia cell lines and patients. We have shown that both drugs can decrease genomic cytosine methylation levels and also affect DNA methylation patterns at selected candidate genes. More recently, we have shown that azacytidine induces RNA demethylation at specific sites, and thus established a novel pathway and a quantifiable biomarker for azacytidine drug activity.

In this project, we will explore the relationship between drug-induced DNA and RNA demethylation in myeloid leukemia cell lines and patients. We will use genome-wide DNA methylation analysis and RNA methylation analysis to comprehensively analyze the methylation patterns in various experimental settings. In addition, we will also analyze the function of the DNMT2 RNA methyltransferase in the epigenetic regulation of human cancer cells.
Our results will provide detailed insights into the epigenetic effects of azacytidine and decitabine in myeloid leukemia.

  • Bocker, M.T., Hellwig, I., Breiling, A., Eckstein, V., Ho, A.D., and Lyko, F. (2011). Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood 117, e182-189. PMID:21427290

  • Hagemann, S., Heil, O., Lyko, F., and Brueckner, B. (2011). Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS ONE 6: e17388. PMID:21408221

  • Frank Lyko

    German Cancer Research Center (DKFZ)
    Im Neuenheimer Feld 280
    D-69120 Heidelberg, Germany
    Phone +49-6221-423800
    Fax +49-6221-423802




    Reinhard Liebers
    Tanja Musch
    Günter Raddatz