Pluripotin effectively suppresses the TKI-resistant primary AML leukemia induced by FLT3^ITD/Tet2^-/-. (A) Experimental design of in vivo experiments to test the efficacy of pluripotin in FLT3^ITD/Tet2^-/-–induced AML using ROSACre^ERT2: FLT3^ITD:Tet2^fl/fl mice. (B) Survival curve showing the significant protection of mice with treatment with pluripotin compared with gilteritinib-treated cohort. (C-D) Shown are weekly progression of leukemic cells (CD45.2) and WBC from the PB of mice treated with gilteritinib and pluripotin. Note, pluripotin treatment effectively suppressed the leukemic progression compared with gilteritinib. Weekly blood counts, total red blood cells (RBCs) (E), hematocrit (HCT) (F), and platelets (G) did not show any adverse effect on hematopoiesis suggesting that pluripotin will be safe and effective. Presented data are from 2 independent experiments (5 mice per group) shown as mean ± SD. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001.