Increasing S100A9 levels in vivo prolongs survival and promotes maturation of leukemic cells. (A) Overview of experimental design. (B) Kaplan-Meyer survival analysis of AML secondary recipient mice treated with 20 µg/mouse rmS100A8, rmS100A9, or PBS 3 times per week until moribund. (C) Weight evolution of AML recipients treated with rmS100A8, rmS100A9, or phosphate buffer saline (PBS; n = 9 for each group). (D) Leukemic cells in peripheral blood (PB) of control and rmS100A9-treated mice during AML progression after 4 weeks posttransplantation (n = 4). (E) CD11b⁺Gr-1⁺ AML population in BM, PB, and spleen in mice untreated or treated with rmS100A9 (n = 6). (F) Representative May-Grunwald-Giemsa–stained cytospins of AML cells from rmS100A9-treated mice showing signs of granulocytic differentiation. Scale bars, 20 µm. (G) Cell-cycle profiles of BM cells from control and rmS100A9-treated recipients (n = 5). (H) Schematic of experimental design for (I) and (J). (I) Survival curves of secondary AML mice injected at day 15 with 10 mg/kg anti-S100A8 or 20 µg/mouse rmS100A9 3 times per week or treated with chemotherapy using cytarabine (100 mg/kg) for 5 days and anthracycline (doxorubicine 3 mg/kg) for 3 days. (J) Mouse weight fluctuation over time in the different treatment protocols (n = 6 per group). (K) CD11b⁺Gr-1⁺ in H9M1 leukemic cells treated with rmS100A9 in the presence or absence of rmS100A8 ex vivo. Results are represented as the mean ± standard error of the mean. P value was determined by Student t test. *P < .05, **P < .01, or ***P < .001 from 3 independent experiments. ns, not significant.