Antileukemic effects of AMPK activators. (A) BV173 or BV173R cells were treated for 5 days with the indicated concentrations of AICAR (mM), and cell viability was determined by methyl-thiazolyl-tetrazolium assays. Data are expressed as percentage control cells and represent mean ± SE of 4 experiments. (B) BV173 and BV173R cells were treated for 5 days with the indicated concentrations of metformin (mM), and cell viability was determined by methyl-thiazolyl-tetrazolium assays. Data are expressed as percentage control cells and represent mean ± SE of 4 experiments. (C) K562, KT1, and BV173 cells were treated with increasing concentrations of AICAR (mM) for 72 hours, as indicated. Apoptosis was assessed by annexin V/PI staining. Data represent mean ± SE of 4 experiments. (D) Ba/F3 cells stably expressing WT-BCR-ABL or T315I-BCR-ABL were treated with either AICAR (mM) or imatinib mesylate (1μM) for 72 hours, as indicated. Apoptosis was assessed by annexin V/PI staining. Data represent mean ± SE of 4 experiments. (E) BV173R cells expressing the T315I mutation were treated with the indicated concentrations of AICAR (mM) or imatinib (5μM) for 72 hours, as indicated. Apoptosis was assessed by annexin V/PI staining. Data are mean ± SE of 4 experiments. (F-G) Effects of different concentrations of AICAR (mM; F), metformin (mM; G), and imatinib mesylate (1μM) on primary leukemic progenitor colony formation (CFU-GM) from CML patients in clonogenic assays in methylcellulose. Data are expressed as percentage control leukemic CFU-GM colony formation of untreated samples and represent mean ± SE of 7 experiments for panel F and 9 experiments for panel G.