Project Grant K08CA304374

The National Cancer Institute awarded Dana-Farber Cancer Institute, Inc. $233,478 on September 1, 2026, under the Cancer Research Manpower program (CFDA 93.398) to characterize and target acquired resistance to menin-KMT2A inhibitors in acute myeloid leukemia.

The award funds research profiling patient samples and patient-derived xenograft models to identify gain-of-function mutations in an oncogenic chromatin complex composed of menin, KMT2A, and PSIP1 proteins that confer resistance to menin inhibitor therapy. The research will determine how these mutations resist menin inhibitor-induced gene expression and chromatin occupancy changes, and will perform biochemical studies to demonstrate that the mutations strengthen protein-protein binding affinities. The work also addresses menin inhibitor resistance that develops through alternative mechanisms, including minimal residual disease states arising in treated patients and xenograft models.

The performance period runs through August 31, 2031, with work performed in Boston, Massachusetts. The Cancer Research Manpower program supports biomedical training opportunities for individuals pursuing careers in basic, clinical, and prevention research relevant to the National Cancer Program, with grants made for periods up to five years and renewable competitive awards subject to peer review and National Cancer Advisory Board evaluation.