Figure 5.
Dasatinib inhibits proliferation of CBL-mutated CMML patient samples in vitro and in vivo. (A) Schematic of the experimental workflow of CMML xenotransplantation model system. (B) Genes mutated in 4 CMML patient samples used for in vitro and in vivo experiments. (C) Percentage change in colony formation with 250 nM dasatinib compared with DMSO after 2 weeks of treatment (mean and SD of 3-4 replicate wells are depicted). (D) Representative images of colony formation by CMML patient sample 2 after 2 weeks in the presence of DMSO or 250 nM dasatinib. (E) Percentage change in human CD45+ cells in the spleens of NSG-S mice engrafted with CMML patient samples and treated with vehicle or 50 mg/kg dasatinib via oral gavage over 2 weeks (mean and SD of 3-5 mice per group are depicted). (F) Anti-hCD45 immunohistochemistry in spleen tissue sections from mice engrafted with CMML patient sample 2 and treated with vehicle or dasatinib for 10 days. Anti-human CD45 stain; scale bar, 70 μM; original magnification ×100. P values were determined by 2-tailed Student t test comparing the mean for vehicle treatment to each dasatinib-treated well or mouse. BM MNC, bone marrow mononuclear cell.