KPT-9274 decreases disease burden and infiltration in a PDX model of AML. (A) Mice with confirmed engraftment were treated for 4 weeks with 150 mg/kg of KPT-9274 oral gavage, once daily (n = 7) or vehicle control (n = 8). (B) At the end of the study, human CD33⁺ cells were assessed by using flow cytometry in the bone marrow in both groups. (C) Whole blood analysis of human CD33⁺ cells in mice after 4 weeks. (D-E) Spleen weights of KPT-9274–treated (n = 7) and vehicle-treated (n = 6) mice. (F) Histology images from PDX mice after 4 weeks of treatment with KPT-9274 or vehicle control. Mice treated with KPT-9274 showed the least severe infiltration of liver, spleen, and bone marrow, whereas infiltration of the liver was often absent in this group (liver, spleen, and bone marrow: 40× magnification, hematoxylin and eosin stain). Vehicle-treated mice had the most severe infiltration of the spleen, bone marrow, and liver. Differentials were performed on cytospins of bone marrow aspirates, which showed myeloid differentiation and fewer blasts in KPT-9274–treated mice vs the vehicle control group (100× oil objective, Wright-Giemsa stain). Leukemia cells are indicated with asterisks (*). (G) Assessment of CD34⁺/CD38^– fraction of leukemic cells in vehicle-treated and KPT-9274–treated mice. (H) Colony formation assays of KPT-9274–treated mouse samples vs vehicle control group after primary, secondary, and tertiary replating. BM, bone marrow.