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Evil Enhancers in AML
Ruud Delwel11Department of Hematology, Erasmus Cancer Institute, Rotterdam, The Netherlands
The discovery that chromatin regulators are often susceptible to small molecule inhibition make cancers with such mutations attractive for epigenetic targeting, as dysregulated enhancers are dependent on these chromatin regulators. We uncovered the frequent hijacking of various enhancers by the oncogene EVI1 in acute myeloid leukemia. Those AMLs, which depend on EVI1 for survival and growth, are mostly incurable. We aim to unravel the mechanisms of EVI1 activation via the hijacked super-enhancers (SEs) in AML. The enhancers that are frequently hijacked by EVI1, can also be translocated to other oncogenes in distinct AML subtypes. Thus studying AML with overexpression of the EVI1 oncogene as the result of SE-hijacking, will serve as a model for a large group of mostly therapy resistant AMLs where oncogenic hijacking of SEs is a central driving mechanism. I will discuss the mechanism of action of those hijacked SEs as well as possible ways to identify small molecules that are able to interfere with the function of the enhancers and consequently inhibit EVI1 expression.
Speakers
Ruud Delwel