Improvement of hepatosplenomegaly and EMH in V617F-TG mice treated with R723 for 6 weeks. (A) R723 effects on liver and spleen weights after R723 treatment for 6 weeks. Liver and spleen weights in V617F-TG mice treated with vehicle (TG-vehicle) were increased compared with those in WT mice treated with vehicle (WT-vehicle) (†P < .01). R723 treatment in V617F-TG mice significantly reduced organ weights (**P < .01). Data are presented as means ± SE. (B) Hematopoietic compartment of spleen assessed by FACS. The proportion of Mac-1/Gr-1⁺ myeloid cells significantly increased, and that of B220⁺ B cells decreased in 18-week-old TG-vehicle mice compared with age-matched WT-vehicle mice (†P < .01). R723 treatment in V617F-TG mice for 6 weeks decreased the proportion of Mac-1/Gr-1⁺ myeloid cells and increased the proportion of B220⁺ B cells (*P < .05). The percentage of CD3⁺ T cells was constant. Data are presented as means ± SE. (C) Histological changes in V617F-TG mice by R723 treatment for 6 weeks. Histology of WT-vehicle and V617F-TG mice treated with vehicle, 35 mg/kg, and 70 mg/kg doses of R723 (TG-vehicle, TG-35mg/kg, TG-70mg/kg, respectively). Cells were stained with H&E. In the spleens of the TG-vehicle mice, the red pulp was expanded with maturing myeloid cells and megakaryocytes and the white pulp was scarce compared with WT-vehicle mice (i-ii). Mice treated with R723 for 6 weeks showed marked reduction of myeloid cell invasion and partially restored architecture (iii-iv). Liver and lung sections from TG-vehicle also displayed EMH (vi and x). Infiltration of myeloid cells disappeared with R723 treatment in V617F-TG mice (vii,viii,xi,xii).