Figure 4
Figure 4. Effect of CYT387 on hematopoietic cell lineages in MPN in vivo. Balb/c mice were subjected to bone marrow transplantation with bone marrow donor cells retrovirally transduced to express JAK2V617F. Thirty-four days after transplantation, mice exhibited symptoms of MPN as measured by elevated white blood cell counts and hematocrit. Mice were divided into 3 groups and initiated on twice daily oral gavage administration of vehicle control, 25 mg/kg CYT387, or 50 mg/kg CYT387 (n = 12 per group). At day 83 after bone marrow transplantation, all mice were sacrificed and spleen and bone marrow cells were stained with fluorescently conjugated antibodies specific for: (A) Gr1 (Granulocytes), (B) CD19/B220 (B cells) and CD3 cells (T cells), (C) CD71 (early erythroid progenitors) and Ter119 (late erythroid progenitors), (D) cKit+CD34− (stem cells/early progenitors) and cKit+CD34+ (late progenitors), (E) CD41 (megakaryocytes). Values represent mean ± SEM and *P < .05 in a t test comparing 25 mg/kg or 50 mg/kg treatment groups with the 0 mg/kg vehicle control. A complete list of numerical values and statistical analyses is found in supplemental Table 2. Representative dot plots are found in supplemental Figure 4.

Effect of CYT387 on hematopoietic cell lineages in MPN in vivo. Balb/c mice were subjected to bone marrow transplantation with bone marrow donor cells retrovirally transduced to express JAK2V617F. Thirty-four days after transplantation, mice exhibited symptoms of MPN as measured by elevated white blood cell counts and hematocrit. Mice were divided into 3 groups and initiated on twice daily oral gavage administration of vehicle control, 25 mg/kg CYT387, or 50 mg/kg CYT387 (n = 12 per group). At day 83 after bone marrow transplantation, all mice were sacrificed and spleen and bone marrow cells were stained with fluorescently conjugated antibodies specific for: (A) Gr1 (Granulocytes), (B) CD19/B220 (B cells) and CD3 cells (T cells), (C) CD71 (early erythroid progenitors) and Ter119 (late erythroid progenitors), (D) cKit+CD34 (stem cells/early progenitors) and cKit+CD34+ (late progenitors), (E) CD41 (megakaryocytes). Values represent mean ± SEM and *P < .05 in a t test comparing 25 mg/kg or 50 mg/kg treatment groups with the 0 mg/kg vehicle control. A complete list of numerical values and statistical analyses is found in supplemental Table 2. Representative dot plots are found in supplemental Figure 4.

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