In vivo administration of dasatinib combined with chemotherapeutic agents enhances elimination of AML stem cells in a murine AML model. (A) Murine AML cells (5 × 10⁴) coexpressing CBFβ–smooth muscle myosin heavy-chain and murine stem cell virus-internal ribosome entry site-green flourescent protein-myeloproliferative leukemia virus oncogene (MIG-Mpl) were injected to wild-type C57BL/6N mice via tail vein. Mice were treated 7 to 10 days posttransplantation with dasatinib alone (10 mg/kg per day) for 5 days, Ara-C (100 mg/kg per day) for 5 days with doxorubicin (3 mg/kg) for 3 days, or the combination of dasatinib with Ara-C and doxorubicin for 5 days. Untreated mice were studied as controls. AML engraftment was assessed by the percentage of GFP⁺ cells in the BM, SP, and PB. BM cells were injected for secondary transplant and mice were followed-up for survival for 240 days. (B) Representative images for the spleen from mice treated in vivo (left) and histogram showing the spleen weight (right). In the different groups (control and dasatinib, n = 8; doxo + Ara-C group, n = 7; and combination group, n = 6). One-way ANOVA with posttest: ns, nonsignificant; *P < .05; ****P < .0001. (C) Absolute number of GFP⁺ cells in BM (left) and SP (right) in each treatment groups. One-way ANOVA with posttest: ns, nonsignificant; **P < .039; ***P < .001; ****P < .0001. (D) Survival curve of mice receiving secondary transplantation of equal numbers of BM cells from control or treated mice (control 900 GFP⁺ cells/mouse, dasatinib 8550 GFP⁺ cells/mouse, chemotherapy 1195 GFP⁺ cells/mouse, dasatinib plus chemotherapy 1160 GFP⁺ cells/mouse). Mice were followed-up for survival up to 240 days (control and dasatinib group, n = 10; doxo + Ara-C and combination group, n = 11); ***P < .001 (Mantel-Cox test).