title: Metabolic characterization of imatinib-resistant BCR-ABL T315I chronic myeloid leukemia cells indicates down-regulation of glycolytic pathway and low ROS production.
abstract: Long-term imatinib treatment induces drug-resistant chronic myeloid leukemia (CML) cells harboring T315I gate keeper mutation of breakpoint cluster region (BCR)-ABL oncogenic kinase. However, although cell proliferation is coupled with cellular energy status in CML carcinogenesis, the metabolic characteristics of T315I-mutant CML cells have never been investigated. Here, we analyzed cell proliferation activities and metabolic phenotypes, including cell proliferation, oxygen consumption, lactate production, and redox state in the KBM5 (imatinib-sensitive) and KBM5-T315I (imatinib-resistant) CML cell lines. Interestingly, KBM5-T315I cells showed decreased cell proliferation, lactate production, fatty acid synthesis, ROS production, and down regulation of mRNA expression related to ROS scavengers, such as SOD2, catalase, GCLm, and GPx1. Taken together, our data demonstrate that the lower growth ability of KBM5-T315I CML cells might be related to the decreased expression of glycolysis-related genes and ROS levels, and this will be used to identify therapeutic targets for imatinib resistance in CML.
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Byung Woong
authors: BW
authors: Ko
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Jeongsu
authors: J
authors: Han
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;|b Brain Research Institute , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Jun Young
authors: JY
authors: Heo
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Yunseon
authors: Y
authors: Jang
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Soo Jeong
authors: SJ
authors: Kim
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Jungim
authors: J
authors: Kim
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Min Joung
authors: MJ
authors: Lee
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;|c Research Institute for Medical Science , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Min Jeong
authors: MJ
authors: Ryu
authors: d Division of Hematology/Oncology, Department of Internal Medicine , Chungnam National University Hospital , Deajeon , Republic of Korea ;
authors: Ik Chan
authors: IC
authors: Song
authors: e Research Center for Endocrine and Metabolic Diseases , Chungnam National University School of Medicine , Deajeon , Republic of Korea.
authors: Young Suk
authors: YS
authors: Jo
authors: a Department of Biochemistry , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;|c Research Institute for Medical Science , Chungnam National University School of Medicine , Daejeon , Republic of Korea ;
authors: Gi Ryang
authors: GR
authors: Kweon
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: Chronic myeloid leukemia; T315I mutant; glycolysis; imatinib resistance; reactive oxygen species