Defining epigenetic mechanisms in NPM1c mutant leukemia

The project will develop a comprehensive understanding of the chromatin state in the presence of NPM1c mutations, specifically focusing on the roles of Menin and MLL. This includes determining changes in chromatin state upon NPM1c degradation and identifying essential protein domains of NPM1c. It will also identify transcriptional activators and chromatin modifiers that associate with the Menin-MLL complex in NPM1c mutant leukemias, leading to aberrant target gene activation. Finally, the project will investigate the chromatin binding factor LEDGF, which associates with Menin-MLL and recruits transcriptional activators, to understand its dependency in NPM1c mutant leukemia cells and its interaction with Menin-inhibition.