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Fig. 7 BRD0705 impairs colony formation in AML cell lines and patient cells and shows in vivo efficacy in multiple AML mouse models. BRD0705 impairs colony formation in AML cell lines and patient cells and shows in vivo efficacy in multiple AML mouse models. (A to C) Colony formation assay of the indicated AML cell lines (A), five primary AML samples (B), and human CD34 cells (C) after BRD0705 treatment. Data are represented as means ± SEM of three replicates. (D) MLL-AF9 cells (250,000) injected into secondary recipient mice after 24 hours of pretreatment with DMSO, BRD0705, BRD3731, or BRD0320. Kaplan-Meier curves are shown (n = 5 per group). (E) MLL-AF9 cells injected into secondary recipient mice in a serially diluted manner (500,000, 250,000, 100,000, or 50,000 cells). Frequency of LICs calculated using ELDA software. (F) MLL-AF9 AML cells injected into secondary recipient mice 3 days before treatment with vehicle (black) or BRD0705 at 30 mg/kg (red). Kaplan-Meier curves for each group of mice (n = 5 per group). (G) HL-60–Luc cells injected into recipient mice and treated with vehicle (black) or BRD0705 at 15 mg/kg (red) or 30 mg/kg (blue). Bioluminescence was quantified. (H) Kaplan-Meier curves for each group of mice treated as in (G) (n = 5 per group). (I) MV4-11–Luc cells injected into recipient mice and treated with vehicle (black), BRD0705 (red), BRD3731 (blue), or BRD0320 (dashed blue). Bioluminescence was quantified. Data are means ± SEM. *P value calculated for the latest time point. (J) Kaplan-Meier curves for each group of mice (n = 10 per group). P < 0.05 determined by log-rank (Mantel-Cox) test in comparison with vehicle. Florence F. Wagner et al., Sci Transl Med 2018;10:eaam8460 Published by AAAS
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