title: Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.
abstract: The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Kawasoe
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Funato
authors.forename: Mayu
authors.initials: M
authors.lastname: Takeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arioka
authors.forename: Masao
authors.initials: M
authors.lastname: Takemura
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Matsunami
authors.forename: Sanford P
authors.initials: SP
authors.lastname: Markey
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004790:Enzyme Induction; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D007938:Leukemia / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011355:Prodrugs / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D050697:Retinal Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D011355:Prodrugs; D034741:RNA, Small Interfering; D003561:Cytarabine; D004317:Doxorubicin; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase; D015255:Idarubicin