Inhibition effects on FLT3/ITD-GFP-32D cells in C3H/Hej-mice syngeneic transplantation model. (A) C3H/Hej mice were inoculated with 2 × 106 of FLT3/ITD-GFP-32D cells on day 0. From the 10th day after inoculation, mice were administrated with KW-2449 at 40 mg/kg (orally) twice a day, AraC at 150 mg/kg (intravenously) daily or vehicle for 4 days (n = 5 in each group). PB was collected from each mouse on day 7 and day 13. BM was collected on day 13. (B) Human FLT3 transcripts in PB were quantitated by a real-time fluorescence detection method. Mean transcript level ± SEM is shown. KW-2449 treatment significantly repressed the expansion of FLT3/ITD-GFP-32D cells compared with AraC treatment (P = .026 by the repeated-measures analysis of variance method). (C) The percentage of residual BM FLT3/ITD-GFP-32D cells in femur was compared among vehicle-, KW-2449-, and AraC-treated mice using flow cytometry. Representative results of flow cytometry are shown. (D) Mean percentages of residual FLT3/ITD-GFP-32D cells plus or minus SD in BM are shown. KW-2449 significantly eradicated FLT3/ITD-GFP-32D cells from BM compared with AraC treatment (P = .009 by the Mann-Whitney U test). (E) Mean spleen weight of each treated mouse ± SD is shown. The mean spleen weight of KW-2449-treated mice was significantly lighter than that of AraC-treated mice (P = .009 by the Mann-Whitney U test). (F) Mean total cell numbers in femur after the treatment ± SD are shown. The total number of nuclear cells in the BM of AraC-treated mice was significantly decreased compared with that of KW-2449–treated mice (P = .016 by the Mann-Whitney U test).
