Prolonged XPO1 inhibition is necessary to elicit significant antileukemic activity in NPM1-mutated AML in vivo. (A) Schematic overview of the in vivo experiments. Each NSG mouse was transplanted with 1 × 10⁶ GFP-Luc⁺ PDX cells. (B) HOXA9, HOXA10, MEIS1, and PBX3 expression by qPCR in sorted PDX2 cells after 7 days of treatment with the vehicle, selinexor 5 mg/kg 2 days per week, selinexor 5 mg/kg 5 days per week, or eltanexor 10 mg/kg 5 days per week. N = 4 mice per group, mean ± SEM, Dunnett multiple comparison test. (C) Flow cytometry quantification of human CD11b, expressed as MFI FC relative to vehicle in sorted PDX2 cells after 7 days of treatment with the vehicle, selinexor 5 mg/kg 2 days per week, selinexor 5 mg/kg 5 days per week, or eltanexor 10 mg/kg 5 days per week. N = 4 mice per group, mean ± SEM, Tukey multiple comparison test. (D) Bone marrow (BM) engraftment of PDX2 cells measured as human CD45 percentage of positive cells after 2 weeks of treatment with the vehicle, selinexor 5 mg/kg 2 days per week, selinexor 5 mg/kg 5 days per week, or eltanexor 10 mg/kg 5 days per week. N = 3 mice per group, mean ± SEM, Tukey multiple comparison test. (E) Representative images of BM histological sections stained for human CD45 after 14 days of treatment with the vehicle, selinexor 5 mg/kg 2 days per week, selinexor 5 mg/kg 5 days per week, or eltanexor 10 mg/kg 5 days per week. Original magnification ×40; scale bars, 20 μm. (F) Representative bioluminescence images of NSG mice transplanted with PDX2 cells treated with either the vehicle (N = 6) or eltanexor 10 mg/kg (N = 7) 5 days per week for 4 weeks. (G) The Kaplan-Meier curves of PDX2 mice treated with either vehicle (N = 6) or eltanexor 10 mg/kg (N = 7) 5 days per week for 4 weeks. Treatment time is shown in light gray. Log-rank (Mantel-Cox) test. (H) Representative bioluminescence images of NSG mice transplanted with PDX3 cells and treated with either the vehicle (N = 6) or eltanexor 10 mg/kg (N = 7) 5 days per week for 4 weeks. (I) The Kaplan-Meier curves of PDX3 mice treated with either vehicle (N = 6) or eltanexor 10 mg/kg (N = 7) 5 days per week for 4 weeks. Treatment time is shown in light gray. Log-rank (Mantel-Cox) test. HR; hazard ratio.