RT Journal Article SR Electronic T1 Inhibition of c-Abl with STI571 Attenuates Stress-Activated Protein Kinase Activation and Apoptosis in the Cellular Response to 1-β-d-Arabinofuranosylcytosine JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1489 OP 1495 DO 10.1124/mol.61.6.1489 VO 61 IS 6 A1 Deepak Raina A1 Neerad Mishra A1 Shailendra Kumar A1 Surender Kharbanda A1 Satya Saxena A1 Donald Kufe YR 2002 UL http://molpharm.aspetjournals.org/content/61/6/1489.abstract AB The response of myeloid leukemia cells to treatment with 1-β-d-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine kinase and the stress-activated protein kinase (SAPK). The present studies demonstrate that treatment of human U-937 leukemia cells with ara-C is associated with translocation of SAPK to mitochondria. STI571 (imatinib mesylate), an inhibitor of c-Abl, blocked both activation and mitochondrial targeting of SAPK in the ara-C response. In concert with these effects of STI571, similar findings were obtained in c-Abl–deficient cells. The results further show that STI571 inhibits ara-C–induced loss of mitochondrial transmembrane potential, caspase-3 activation, and apoptosis. These findings demonstrate that STI571 down-regulates c-Abl–mediated signals that target the mitochondria in the apoptotic response to ara-C.