We study the molecular-genetic background of leukemia, with a focus on myelodysplastyic syndromes (MDS) and acute myeloid leukemia (AML). We investigate the genetic, pathogenic mutations and their downstream molecular and cellular consequences in several model systems. Specifically, we focus on genes that are implicated in the regulation of gene expression such as transcription factors, epigenetic regulators and splicing factors. Apart from the molecular and cellular consequences, the relevance of these mutations in therapy response, relapse and prognosis are assessed. Finally, we study the mechanisms behind the expansion and genetic evolution from pre-malignant, malignant and finally therapy-resistant clones of cells, in order to find clues for prevention of leukemia development and/or disease progression.