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. 2022 Sep 16;8(37):eabp9005. doi: 10.1126/sciadv.abp9005

Fig. 9. The combination therapies of dinaciclib (CDK9i), PRT808 (PRMT5i) or brequinar (DHODHi), and gilteritinib manifest superior efficacy in a FLT3-ITD AML xenograft model.

Fig. 9.

(A) NCG mice were engrafted with MOLM-13 cells expressing luciferase and received different treatments. In the first cohort, mice received vehicle, dinaciclib (10 mg/kg) weekly, gilteritinib (30 mg/kg) daily, and dinaciclib/gilteritinib combination. In the second cohort, mice received vehicle, gilteritinib (15 mg/kg) daily, brequinar (25 mg/kg) for a total of six doses, PRT808 (5 mg/kg) chow daily, brequinar/gilteritinib combination, or PRT808/gilteritinib combination. Control high-fat chow was given to all non-PRT808 mouse groups. (B and C) IVIS imaging shows changes in luciferase signal over study periods. (D) Kaplan-Meier curves of the mouse survival times in different treatment groups. The number of mice per group was indicated. ***P < 0.001 and ****P < 0.0001. (E and F) Combination therapy significantly reduced spleen weight of engrafted mice. Statistical significance of differences in spleen weights between groups were estimated using ANOVA methods. P values have been adjusted for multiple comparisons using Holm’s procedure. *P < 0.05 and ***P < 0.001. Mice in (F) received high-fat chow. (G) Morphology scores of cytospins of enriched human cells from mouse spleens in different treatment groups. (H) Weight changes of mice in different treatment groups over 30 days.