SIRT3 inhibition perturbs leukemia stem cell function and spares normal hematopoietic stem and progenitor cells. (A) Colony-forming ability of reactive-oxygen species (ROS) low leukemia stem cells (LSC) was assessed from 6 primary acute myeloid leukemia (AML) (AML 4, 5, 7, 8, 9, 14) and treated with YC8-02 for 24 hours at increasing doses, when possible, prior to performing the colony-forming unit (CFU) assay. Each dot represents a unique AML. Statistical significance was determined using ordinary one-way ANOVA. (B) Colony-forming ability of representative mobilized peripheral blood cells (MPBC) following treatment with YC8-02 for 24 hours at increasing doses prior to performing the CFU assay. Statistical significance was determined using two-way ANOVA. (C) Serial colony-forming ability of primary AML 7, 9, 10, and 24 treated with 10 µM YC8-02 for 24 hours. Each dot represents a unique AML. Statistical significance was determined using an unpaired t-test. (D) Serial colony-forming ability of normal bone marrow treated with 10 µM YC8-02 for 24 hours. Statistical significance was determined using an unpaired t-test. (E) Engraftment of 3 primary AML treated with YC8-02. Each point represents a single mouse. Statistical significance was determined using an unpaired t-test. (F) Engraftment of 2 normal bone marrow specimens in NSG-SGM3 mice following treatment with YC8-02. Each point represents a single mouse. Statistical significance was determined using an unpaired t-test. All error bars represent standard deviation. *P<0.05, **P<0.01, ***P<0.005, ****P<0.001; ns: not significant.