Dnmt3a^R878H/+ HSCs are the most potent cell of origin transformed by Npm1^cA. (A) Experimental design. (B) Overall survival of mice transplanted with Dnmt3a;Npm1-mutant HSCs (n = 5), MPP^G/M (n = 3), MEP (n = 6), or GMP cells (n = 5). *P < .05 by Kaplan-Meier. (C) Blood, BM, spleen, and liver data collected from individual moribund mice used for blinded diagnoses of hematologic malignancies. (D) Somatic mutations detected in individual BM samples using M-IMPACT targeted sequencing.