CX-5461 therapy delays disease progression and significantly extends survival in leukemic mice. (A) Leukemia progression and engraftment of M/E p53WT and M/A9 p53WT AML in recipient C57Bl/6 mice was followed by bioluminescence imaging at day 7 (7 d, baseline), 14 (14 d), and 21 (21 d) posttransplant (pt). Representative images of n = 10 per group. (B) Kaplan-Meier survival curves for CX-5461 (40 mg/kg every 3 days, start of therapy day 7 pt, last dose day 28 pt in M/E p53WT, and last dose day 20 pt in M/A9 p53WT); cytarabine/doxorubicin (5 days of 50 mg/kg cytarabine in combination with the first 3 days of 1.5 mg/kg doxorubicin, start of therapy day 7 pt, and last dose day 11 pt) and vehicle-treated leukemic mice (M/E p53WT median survival, 17 days for vehicle vs 36 days for CX-5461, P < .0001; M/A9 p53WT median survival, 13 days for vehicle vs 24 days for CX-5461, ****P < .0001; n = 8 to 10 per group). (C) WBC prior to therapy initiation and after 3 doses of CX-5461 treatment (****P < .0001; n = 8 to 10 per group). (D) Spleen weights of mice when euthanized (****P < .0001; n = 8 to 10 per group; WT nonmalignant). (E) Overall survival of CX-5461 (40 mg/kg every 3 days, 6 doses total, start of therapy day 20 pt, and last dose day 35 pt) and vehicle-treated AML1/ETO9a Nras p53WT leukemia-bearing mice (****P < .0001; n = 10 per group). (F) GFP⁺ circulating tumor cells prior to therapy and after 3 doses of treatment in the peripheral blood of leukemic mice (AML1/ETO9a Nras p53WT (****P < .0001; n = 7 to 10 per group). Gray indicates time of CX-5461 and vehicle treatment (B,E). Log-rank test (B,E) and unpaired 2-tailed Student t test were performed (C,D,F). Graphs represent mean ± SEM. Cyt, cytarabine; d, day; Dox, doxorubicin.