Genetic landscape of comutations in NPM1-mutated acute myeloid leukemia and their prognostic impact on MRD (NPM1 transcripts, peripheral blood assessment after cycle 2), incidence of relapse, and overall survival. When considered in isolation, the poorer prognostic value of FLT3-ITD is fully captured by MRD (ie, FLT3-ITD–positive patients with negative MRD do not have an excess in relapse or death risk). However, when considering all comutations, patients with ≥2 genes mutated among FLT3-ITD, DNMT3A, and WT1, or patients with non-ABD NPM1 variants have a higher risk of relapse or death, even when they achieve MRD negativity. Professional illustration by Patrick Lane, ScEYEnce Studios.