KPT-330 treatment increases survival time of leukemic mice. (A) Nested RT-PCR for BCR-ABL1 mRNA in the PB measured 1, 10, and 16 weeks after injection. PB of age-matched mice (NC) and a 1:106 dilution of 32D-BCR/ABL cells with 32Dcl3 cells were used as negative and positive controls, respectively. GAPDH mRNA levels were used as a control. (B) Gross anatomy of spleens isolated from vehicle- and KPT-330–treated (15 mg/kg, 2 times weekly) mice injected with 32D-BCR/ABL cells, age-matched controls, and/or KPT-330 only–treated mice at 5 weeks (top panel) and 16 weeks (bottom panel) after cell-injection. (C) Kaplan-Meier curve shows effect of KPT-330 treatment (15 mg/kg, 2 times weekly) on survival of SCID mice injected with 32D-BCR/ABL cells (n = 10, red line). Untreated mice injected with cells (n = 8, blue line) or KPT-330–treated mice that did not receive cells (n = 7, green line) were used as controls. Survival was calculated by the Kaplan-Meier method, and the log-rank test evaluated the differences among survival distributions: P = .002 (32D-BCR/ABL–untreated vs 32D-BCR/ABL KPT-330–treated mice). (D) Wright/Giemsa staining of PB and H&E staining of sections from the BM, spleen, and liver of untreated and KPT-330–treated control and cell-injected mice.
