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Src family kinase inhibitor PP2 enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide
Authors:Yun Seok Jung  Hee-Jeong Cheong  Sook-Ja Kim  Kyoung Ha KimNamsu Lee  Hee Sook ParkJong-Ho Won
Institution:Division of Hematology-Oncology, Department of Internal Medicine, and Institute for Clinical Molecular Biology Research, Soonchunhang University College of Medicine, Soonchunhang University Seoul Hospital, Seoul, Republic of Korea
Abstract:An all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) combination yields high-quality remission and survival in newly-diagnosed acute promyelocytic leukemia (APL). For subsequent similar data, NCCN guidelines indicate that ATRA plus ATO is one of the recommended regimens for the treatment of patients with APL. We demonstrated SFK (Src family kinase) inhibitor PP2-enhanced APL cell differentiation when combined with either ATRA or ATO with difference in activation of RA-induced genes. In this study, we investigated whether SFK inhibitor PP2 could enhance the differentiation of NB4 APL cells when combined with ATRA and ATO and the changes in the expression of intercellular adhesion molecule-1 (ICAM-1) derived from the retinoic acid receptor (RAR) target gene.
Keywords:Acute promyelocytic leukemia  All-trans retinoic acid  Arsenic trioxide  Src kinase  Differentiation
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