Taking the direct route: menin inhibitors go straight to the frontline in KMT2A-rearranged acute leukemia.

Menin inhibitors disrupt oncogenic transcription in KMT2A-rearranged leukemias, but responses are heterogeneous. A previous study highlighted the role of nongenetic resistance driven by altered chromatin context, including loss of KMT2C/D-UTX activity, underscoring the need for broader epigenetic profiling to guide therapy timing and combination strategy selection.