M-CSF is required for engraftment of AML with inv(16). (A) Scatter plot compares human engraftment in the bone marrow of mice of the indicated strains transplanted with inv(16) AML. Split samples are indicated by blue (PID330) and red (PID420) symbols (mean ± SD; N = 8-16 per group; Mann-Whitney U test P < .0001 for aggregate NSG vs cytokine KI, P = .01 for PID330, P = .03 for PID420; 1-way ANOVA P = .0002). (B) Mean expression of inv(16), type A normalized to ABL1 in transplanted mice of the indicated strains (mean ± SD, N = 4-7 per group, 1-way ANOVA P < .0001). (C) Brightfield microscopy images depict bone marrow aspirate smear from PID420 at initial diagnosis (left) and cytospins from NSG (middle) and MISTRG (right) mice transplanted with PID420 AML. Bars represent 20 µm. Data are representative of N = 6. (D) Serial transplantation: cartoon shows experimental setup; dot plots show immunophenotype of engrafted human cells. Data are representative of 2 independent experiments. (E) Bar graphs depict expression of indicated cytokine receptors in indicated AML subgroups (non-FR, nonfavorable risk) by microarray analysis (mean ± SD; N = 32-298 per group; 1-way ANOVA P < .0001 for c-Mpl, M-CSF receptor [M-CSFR], and GM-CSF receptor [GM-CSFR]; P = .02 for IL-3Rα). (F) Gene set enrichment analysis of M-CSF inducible genes in inv(16) compared with NPM1A^mut AML (N = 33 for inv(16), N = 46 for NPM1A^mut; enrichment score 0.72, significant at nominal P value <5%).