In vivo SHP2 inhibitor treatment of KITD814V-bearing mice enhances their survival and modulates MPD. (A) Mice received 100 mg/kg II-B08 intraperitoneally each day for 7 days. Mice were harvested after 24 hours of final injection, and peripheral blood, BM, spleen, and thymus were analyzed. Cells from spleen were stained with anti–phospho-SHP2 antibody by intracellular staining and analyzed by flow cytometry. Left panel: representative phospho-SHP2 flow micrographs. Right panel: average percentage of phospho-SHP2-positive cells from 4 mice. A 50% reduction in the phosphorylation of SHP2 was observed in mice treated with II-B08 compared with DMSO. (B) Kaplan-Meier survival analysis of leukemic mice treated with DMSO or II-B08. The 32D cells bearing oncogenic KITD814V were injected into syngeneic C3H/HeJ mice through tail vein. Mice were treated with either vehicle DMSO (n = 5) or II-B08 (50 mg/kg body weight; n = 6) at 12-hour intervals for 14 days. Left panel: schematic of drug treatment model. Right panel: survival curve. Significantly prolonged survival of mice treated with II-B08 was observed compared with mice treated with DMSO. *P < .05. (C-D) Reduced splenomegaly and hepatomegaly in KITD814V-bearing mice treated with II-B08. Average weights (C) and pictures (D) of spleen and liver of mice transplanted with cells bearing oncogenic KITD814V and treated with DMSO or II-B08. Significant reduction in spleen and liver weights was observed in mice treated with II-B08 compared with mice treated with DMSO. n = 5 or 6. *P < .05.