Increased osteoblast numbers suppress AML. (A-G) BALB/c mice at 2 months of age were treated orally, with either vehicle or LP533401 (25 mg/kg of body weight per day), for 4 weeks. WEHI-3B cells were injected on day 14 following the beginning of the treatment. (A-C) H&E staining of sections showing blast infiltration (dotted line) in the marrow of vehicle-treated but normal myeloid and erythroid maturation (continuous line) in the marrow of LP533401-treated mice (inset magnifications of blasts and normal bone marrow are shown in the right panels, and normal megakaryocytes are indicated by white arrows) (A), extensive blast infiltration (black arrows) in the liver of vehicle-treated mice but normal liver morphology in LP533401-treated mice (B), and diffuse blast infiltration of splenic red pulp in vehicle-treated mice (black arrow) but normal red pulp with normal megakaryocytes (white arrow) and myeloid and erythroid colonies in LP533401-treated mice (C). (D-F) Frequency of blast infiltration (D), myeloid hyperplasia (E), and megakaryocyte numbers (F) in the bone marrow of mice treated with vehicle or LP533401 (A-F, n = 10-14 mice per group). (G) Correlation of osteoblast numbers with marrow leukemic blast percentage (n = 7-8 mice per group). (H-M) Syngeneic 2-month-old albino C57BL/6 mice were treated orally with LP533401 (200 mg/kg of body weight per day) or vehicle for 7 days and then injected with DsRed-MLL-AF9 cells and euthanized 12 days following injection. (H) Overall survival of leukemic mice treated with LP533401 or vehicle (n = 12 mice per group). Percentage of MLL-AF9 cells (I) and percentage of MLL-AF9 cells in the S1 phase (J). Percentage of MLL-AF9 cells in the spleen (K) and blood (L). (M) Immunofluorescence staining of spleen sections showing DsRed-MLL-AF9 cells and 4,6-diamidino-2-phenylindole staining (blue) (I-J, n = 5 mice per group). *P < .05 relative to WT vehicle.