New Investigator Research Grant Program

This project will help doctors better use new targeted drugs for a common form of adult leukemia. About one-third of people with acute myeloid leukemia (AML) have mutations in a gene called NPM1, and they can now receive recently approved “menin inhibitor” pills such as revumenib and ziftomenib. Unfortunately, many patients do not respond well, and today there is no good way to predict who will benefit or how to overcome resistance. My lab has discovered that a stress-response protein called SIRT7 helps cells sense damage in a structure called the nucleolus and turn on the tumor-suppressor protein p53. In NPM1-mutated AML, this safety system is disrupted, which may allow leukemia cells to survive treatment. We will test whether SIRT7 levels in patient samples can predict response to menin inhibitors, and whether boosting SIRT7 makes these drugs work better in leukemia cells and mouse models. Over two years, we will analyze stored bone marrow samples from AML patients, perform detailed studies in human leukemia cell lines, and evaluate promising combinations in mouse models. If successful, this work will deliver a practical laboratory test to guide menin inhibitor use and lay the groundwork for combination therapies that more effectively eradicate NPM1-mutated AML while minimizing unnecessary treatment.