Acute myeloid leukemia (AML) is a form of blood cancer, which originates in the bone marrow and features an expanded subset of white blood cells, called myeloid cells. The maturation of these myeloid cells requires genetic programming, which is ensured by specific proteins called transcription factors. We have observed that loss of the transcription factor Gfi1, leads to an accumulation of myeloid cells in mice that is reminiscent of a condition that often precedes overt myeloid leukemia. We also have discovered a variant of the Gfi1 gene and that humans that carry this variant have a higher risk to develop AML. We were further able to show that the Gfi1 variant accelerates an experimental AML like disease in mice. and we discovered that the Gfi1 variant associated with AML introduced so called epigenetic alteration in the genome that lead to aberrant gene regulation. We wish to understand the underlying molecular mechanisms that causes these epigenetic changes to better under stand the disease and to eventually prepare the ground for the better therapies.