Prdm16s expression in HSPCs causes AML. (A) Relative expression levels of Prdm16 in murine hematopoietic cells compared with whole bone marrow (WBM) cells (n = 3). (B) Survival of mice after transplanting LSK cells transduced with empty vector (vec; n = 10), Prdm16 (n = 14), or Prdm16s (n = 15). (C) Flow cytometric analysis revealed increased myeloid cells (Mac-1/Gr-1⁺) in the peripheral blood (PB) of recipients transplanted with Prdm16s-transduced LSK cells compared with vector-transduced LSK cells (n = 10). (D-E) Representative images of Wright-Giemsa–stained PB cells (D) and spleens from wild-type (WT) mice and mice transplanted with Prdm16s-transduced LSK cells (E). (F) Increased white blood cells (WBCs; n = 6), decreased red blood cells (RBCs; n = 8), and platelets (PLTs; n = 8) in recipient mice of Prdm16s-transduced cells. (G) Secondary recipients (n = 10) of Prdm16s-transduced cells developed AML with a shorter latency than the primary recipient mice (n = 15). (H) Increased lineage⁻ and lineage⁻Sca-1⁻c-kit⁺ (LK) myeloid progenitor cells in the bone marrow (BM) of recipients transplanted with Prdm16s-transduced cells (n = 5). Flow cytometric plots are gated on lineage⁻ cells. 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. B, B cell; CMP, common myeloid progenitor; Ery, erythrocyte; H&E, hematoxylin and eosin; HPC, hematopoietic progenitor cell; Mk, megakaryocyte; Mye, myeloid cell; ns, not significant; T, T cell.