Fig. 2

In vivo effects of KX2-391 in mice bearing FLT3-ITD-F691L leukemia and against patient leukemic blast cells harboring FLT3-ITD or FLT3-ITD-D835Y mutations. a Kaplan–Meier survival curves of FLT3-ITD-F691L leukemia mice administered vehicle, Gilteritinib (30 mg/kg), AC220 (10 mg/kg), or KX2-391 (10 mg/kg) once daily for 10 days (orally). **** P < 0.0001. b No change in body weight was detected between the KX2-391 treatment and vehicle control groups. c The percentage of GFP-positive Ba/F3 FLT3-ITD-F691L leukemia cells in peripheral blood (PB) samples from mice treated with vehicle, Gilteritinib (30 mg/kg/d), AC220 (10 mg/kg/d), or KX2-391 (10 mg/kg/d) for 4 days and for 8 days. d Representative weight of spleens at 10 days after injection with Ba/F3 FLT3-ITD-F691L leukemia cells, and Flow cytometry analysis of bone marrow cells and spleens from mice as described in (c). e Hematoxylin and eosin staining of spleens and liver from mice treated as described in (a). Scale bars in the panel are 50 μm. f Patient-derived AML leukemic blast cells expressing FLT3-ITD/D835Y (patients 1 and 2), FLT3-ITD (patient 3) and peripheral blood mononuclear cells (PBMCs) from healthy donors were incubated for 48 h with the indicated concentrations of KX2-391 (g), and the cell viability was then determined. For each FLT3 inhibitor, the percentage over DMSO control was presented as a mean value, with error bars representing ± SD. h KX2-391 suppresses FLT3 phosphorylation in primary AML cells incubated for 12 h with the indicated concentrations (based on the IC50 values), as determined by western blotting using the indicated antibodies. GAPDH was used as a loading control. ****P < 0.0001