AML-iPSC–derived hematopoietic cells exhibit cardinal leukemia features. A, AML-iPSCs were differentiated into HSPCs and injected into immunodeficient mice (NSG or NSGS). Human cell engraftment was assessed after 13–15 weeks or earlier if signs of illness. B–D, Levels of human engraftment in the BM, spleen, and blood of NSG and NSGS mice, as indicated, 5 to 22 weeks after transplantation with 1 × 106 HSPCs derived from the indicated AML-iPSC lines. Each data point represents one mouse. Error bars show mean and SEM. E, Fraction of myeloid (CD33+) lineage cells within the hCD45+ population in the BM of mice transplanted with HSPCs derived from the indicated AML-iPSC lines. Each data point represents one mouse. Error bars show mean and SEM. F, Representative flow cytometry analyses from BM of recipient mice transplanted with HSPCs from the indicated AML-iPSC lines. G, Representative image showing marked splenomegaly in 4 mice transplanted with HSPCs from the AML-47.1 line. UT: untransplanted mouse. H, Kaplan–Meier curves showing survival of mice transplanted with HSPCs from the indicated AML-iPSC lines. I, Human engraftment levels in the BM of secondary recipient mice. Each data point represents a unique mouse. Mean and SEM are shown.