Nuclear transcriptional condensates as drivers and therapeutic targets in NPM1-mutated AML.

NPM 1-mutated acute myeloid leukemia (AML) is driven by aberrant HOX/MEIS1 expression, whose mechanistic basis remained unresolved for years. Recent paradigm-shifting studies show that mutant NPM1 organizes phase-separated nuclear condensates that concentrate transcriptional regulators at active chromatin, directly sustaining the pathogenic HOX/MEIS1 transcriptional program. This framework explains the activity of menin-KMT2A inhibitors, recently approved by the US Food and Drug Administration, in this AML subtype and positions disruption of these assemblies as a precision strategy to eliminate oncogenic transcription.