Altered enhancer activity is one of the main drivers of aberrant expression of oncogenes in a subset of patients with acute myeloid leukemia. Upon translocation we observed that enhancers that tightly regulate key-genes important for normal development, may become over-activated and cause uncontrolled expression of their “novel” target gene. We wish to unravel how translocated enhancers in malignant cells can become so-called “super-enhancers”. Using genome editing and novel expression interference technology, we wish to uncover the exact coding-regions within the enhancers and the protein machinery that cause uncontrolled activation of disease genes.
The strength of our research group and department is the excess of large numbers of vitally frozen patient samples, a genome editing core, sequencing facilities, years of experience in culturing primary AMLs cells and development/studying myeloid leukemia in vivo (mouse models).