KPT-9274 increases survival rates and prevents disease migration in an AML xenograft mouse model. (A) Dosing schematic of NSG mice engrafted with MV4-11 luciferase-expressing cells were treated with 150 mg/kg of KPT-9274 (n = 7) or vehicle control (n = 5). (B) Overall survival of KPT-9274–treated mice vs vehicle-treated mice are shown according to Kaplan-Meier analysis. (C) Human CD33⁺/CD45⁺ cells were assessed in the bone marrow at the end of the study by using flow cytometry. (D) Cytology of bone marrow cytocentrifugation preparations (top row; 100× oil objective, Wright-Giemsa stain) and histology of the spleen (bottom row; 60× magnification, hematoxylin and eosin stain) of KPT-9274–treated and vehicle-treated mice who met euthanasia removal criteria and were removed from the study. (E) Disease progression was assessed in a separate cohort of mice treated with KPT-9274 (n = 3) and vehicle control (n = 3) by using IVIS bioluminescence after treatment began. (F) Histopathology of the bone marrow of mice euthanized before mice met early removal criteria (ERC) in KPT-9274–treated and vehicle-treated mice (60× magnification, hematoxylin and eosin stain). Bone marrow from vehicle-treated mice revealed multifocal infiltration by neoplastic myeloid cells, with occasional foci of coagulation necrosis or infarction, presumably due to outgrowth of blood supply (inset). By contrast, mice treated with KPT-9274 showed markedly less or absent infiltration. O.G., oral gavage; q.d., once daily.