Humanized cytokine KI mice support robust engraftment of favorable-risk AML and closely model disease biology. (A) Schematic representation of experimental setup. Scatter plots depict blast count in patients with inv(16) or NPM1^mut AML (left columns) and human engraftment in transplanted NSG or cytokine KI mice, in the bone marrow (B) and peripheral blood (C) (mean ± standard deviation [SD], N = 15-45 per group, 1-way ANOVA P < .0001 for both bone marrow and peripheral blood). Data stem from >20 independent experiments. Scatter plots compare human engraftment in NSG and MI(S)TRG mice transplanted with NPM1^mut AML in the bone marrow (D) and peripheral blood (E) (mean ± SD, N = 19-36 per group). (F) Mean expression of NPM1A^mut allele normalized to PBGD in engrafted NSG and MISTRG mice (mean ± SD, N = 4 per group). (G) Allelic frequency of NPM1 mutation (TCTG insertion at position chr5:170837542) in patient (PID250), transplanted cytokine KI mice (n = 3) and untransplanted cytokine KI mouse (ctrl) when mapping to HG19:chr5:170837542 (human reference genome). (H) Frequency of subclones of NPM1 insertion at HG19:chr5:170837542 in patient (PID250) and 3 cytokine KI mice.