New Investigator Research Grant Program

Acute myeloid leukemia (AML) is an aggressive blood cancer that is primarily treated with chemotherapy, but relapse is common and outcomes remain poor. AML is often driven by genetic abnormalities that produce fusion proteins disrupting normal blood cell development. One such protein, CBFß::MYH11, blocks differentiation and promotes leukemia cell survival. This proposal tests small molecules that target CBFß::MYH11 as a new strategy for treating chemotherapy-resistant AML. In preliminary studies, we developed resistant AML models and showed that the inhibitor AI-10-49 reduces growth and induces death in CBFß::MYH11-positive cells. We also identified additional candidate compounds through virtual screening with strong predicted binding to the fusion protein. We hypothesize that inhibiting CBFß::MYH11 will suppress disease progression in relapsed or refractory AML. The study will evaluate AI-10-49 in cell lines, patient samples, and mouse models, and test new compounds in biochemical and cellular assays. Overall, this work aims to establish a targeted therapeutic approach for AML patients with limited treatment options.