Combination of SIRT1 inhibition with imatinib for treatment of mouse CML. (A-B) Survival curves (A) and total blood leukocyte counts (B) for CML mice treated with drugs. Ten days after receiving 1 × 105 BM cells transduced by MIG210, mice were treated by vehicle, imatinib (200 mg/kg/d), tenovin-6 (50 mg/kg/d), or combination for 10 days. Total blood leukocyte counts were analyzed at day 20 after transplantation. (C) BM cells from CML mice were cultured with 2.5μM imatinib, 1μM tenovin-6, or combination for 3 days, and apoptosis was analyzed for GFP+ cell fraction. DMSO was used as reagent control (CTL). (D) After treating GFP-sorted BM cells from CML mice with imatinib, tenovin-6, or combination for 24 hours, cells were washed and plated in methylcellulose medium without drugs for CFC assay. (E) Effect of combination of SIRT1 knockout and imatinib on CML mouse survival. Wild-type or SIRT1−/− donor BM cells were transduced with MIG210 and 2 × 105 cells were transplanted for each recipient. Imatinib or vehicle was given as described in panel A.
