NIH R01 · 2025
Defining epigenetic mechanisms in NPM1c mutant leukemia
Project Summary/Abstract Nucleophosmin (NPM1) mutations are among the most common aberrations in acute myeloid leukemia (AML) and cause a characteristic stem cell-like gene expression pattern including the upregulation of HOXA/B cluster genes and their co-factors MEIS1. The molecular mechanisms of how NPM1c mutations regulate this aberrant gene expression program remains poorly understood and there are currently no targeted therapy options available. We have recently found that NPM1c mutant leukemias depend on the histone methyltransferase MLL and its adaptor protein Menin to maintain leukemia gene expression and proliferation. The interaction between Menin and MLL is essential for the…
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