Inhibition of SIRT1 sensitizes KRAS-mutant leukemic cells to cytarabine-induced cell death. (A) NB4, Nomo1, and THP1 cells were treated with vehicle, TV-6, and cytarabine (Ara-C) alone or in combination, as indicated. (B) NB4 cells were transduced with lentiviral vectors expressing a doxycycline-inducible nonsilencing miR-shRNA (shScr) or a miR-shRNA targeting SIRT1 (shSirt1), incubated with doxycycline for 72 hours followed by treatment with cytarabine (Ara-C), daunorubicin (DNR), and irradiation (IR; 2 Gy), as indicated. (C) NB4 cells were treated with the selective MEK-inhibitor PD98059 or TV-6 alone or in combination, as indicated. The percentage of sub-G1 cells corresponding to apoptotic cells was determined by flow cytometry. Data represent mean values ± SD of 3 independent experiments. *P < .05, **P < .01, ***P < .001; unpaired Student t test.