Fig. 10

Gilteritinib plus ATO is efficacious in mouse xenograft models of FLT3-ITD mutant AML. a, b Six-week-old female nude mice were subcutaneously injected in the flank with 1 × 10⁷ MV4-11 cells to establish a xenograft model of AML. When tumors were established, mice were treated with daily vehicle, intraperitoneal injection of ATO (1 mg/kg/day), oral administration of Gilteritinib (10 mg/kg/day), or Gilteritinib (10 mg/kg/day) plus ATO (1 mg/kg/d) in combination for 2 weeks. Tumor growth was evaluated by measuring tumors with a caliper. *P < 0.05, Gilteritinib + ATO group vs the Gilteritinib group. ^##P < 0.01, ^###P < 0.001, Gilteritinib + ATO group vs the ATO group. c, d Tumor cells from vehicle group, Gilteritinib group, ATO group and Gilteritinib + ATO group were lysed and analyzed by western blot using indicated antibodies (P-FLT3 and FLT3). ***P < 0.001. e, f Tumor cells from vehicle group, Gilteritinib group, ATO group and Gilteritinib + ATO group were lysed and protein levels of IRE1a, JNK and P-JNK were determined by western blot. *P < 0.05, ***P < 0.001. g Apoptosis was measured in tumor tissue from vehicle group, Gilteritinib group, ATO group and Gilteritinib + ATO group using the TUNEL assay. Green-fluorescence represents apoptosis