Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors.

Patient AML samples positive for NUP98/NSD1 were provided by the Princess Maxima Center for Pediatric Oncology. All samples were also positive for FLT3-ITD with VAFs > 0.35....Treatment of four different NUP98/NSD1-positive AML samples in this setting resulted in a profound dose-dependent inhibition of proliferation with latency of 10 days and IC50 values between 2 and 50 nM.