AML cells with acquired resistance to menin inhibition

Menin inhibition has shown promising clinical results in patients with KMT2A-rearrangement (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML). However, not all patients respond, and resistance to the treatment develops in some patients. To understand the mechanisms of resistance to menin inhibition and develop mechanism-based therapeutic strategies to overcome the resistance, we generated OCI-AML3 (NPM1c) cells with acquired resistance (SNDX-R) to the menin inhibitor SNDX-50469 through prolonged exposure.