MEPs initiate myeloid leukemias upon Prdm16s expression. (A) Flow cytometric plots showing the expansion of MEPs but not GMPs or common myeloid progenitors (CMPs) in mice transplanted with Prdm16s-transduced LSK cells in comparison with vector-transduced cells. Cells are gated on lineage⁻Sca-1⁻c-kit⁺ (LK) cells (n = 10). (B) Survival of mice after transplanting 500 000 GFP⁺ bulk leukemia cells or 50 000 MEPs isolated from primary recipient mice (n = 10). (C) A limiting dilution transplantation assay revealed that L-MEPs are highly enriched for LICs (1 in 29; n = 10). Frequency (Fre), 95% confidence interval (CI), and P value are shown on right. (D) CD34⁻ or CD150⁺ MEPs were isolated from wild-type mice, and transplantation of these cells after transducing with Prdm16s caused myeloid diseases with similar latencies (n = 10). (E-G) Recipient mice (n = 5) of Prdm16s-transduced, but not vector-transduced, MEPs had expansion of myeloid cells compared with recipient mice (E), increased white blood cells (WBCs) and reduced red blood cells (RBCs) and platelets (PLTs) (F), and increased lineage⁻, lineage⁻Sca-1⁻c-kit⁺ (LK), and MEPs (G). All data represent mean ± standard deviation. *P < .05, **P < .01, ***P < .001 by Student t test, except for comparison of survival curves, in which significance was assessed by log-rank test. BM, bone marrow; PB, peripheral blood.