Figure 5
Crenolanib activity against MOLM-13-RES cells in vitro and in vivo. (A-B) MOLM-13-luc and MOLM-13-RES-luc cells were treated with DMSO or increasing concentrations of crenolanib or sorafenib (A) for 72 hours and viability was measured or (B) for 1 hour and lysed. Western blot analysis was performed on FLT3 immunoprecipitation eluent using the indicated antibodies. Cell viability measurements represent the mean ± SEM of 2 to 3 experiments with 6 replicates each (n = 12-18). (C-D) Female NSG mice engrafted with MOLM-13-RES-luc cells were treated with vehicle, sorafenib 15 mg/kg orally once daily, or crenolanib 15 mg/kg intraperitoneally once or twice daily (Monday to Friday) for 3 consecutive weeks beginning on day 3. (C) Leukemic cell bone marrow infiltration was monitored by noninvasive luciferase imaging (**P < .01; ***P < .001). (D) Kaplan-Meier analysis of animal survival (***P < .0001 for crenolanib once daily vs vehicle; ***P < .0001 for crenolanib twice daily vs vehicle). Black bar denotes treatment period.

Crenolanib activity against MOLM-13-RES cells in vitro and in vivo. (A-B) MOLM-13-luc and MOLM-13-RES-luc cells were treated with DMSO or increasing concentrations of crenolanib or sorafenib (A) for 72 hours and viability was measured or (B) for 1 hour and lysed. Western blot analysis was performed on FLT3 immunoprecipitation eluent using the indicated antibodies. Cell viability measurements represent the mean ± SEM of 2 to 3 experiments with 6 replicates each (n = 12-18). (C-D) Female NSG mice engrafted with MOLM-13-RES-luc cells were treated with vehicle, sorafenib 15 mg/kg orally once daily, or crenolanib 15 mg/kg intraperitoneally once or twice daily (Monday to Friday) for 3 consecutive weeks beginning on day 3. (C) Leukemic cell bone marrow infiltration was monitored by noninvasive luciferase imaging (**P < .01; ***P < .001). (D) Kaplan-Meier analysis of animal survival (***P < .0001 for crenolanib once daily vs vehicle; ***P < .0001 for crenolanib twice daily vs vehicle). Black bar denotes treatment period.

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