title: The hENT1 and DCK genes underlie the decitabine response in patients with myelodysplastic syndrome.
abstract: Decitabine is approved for the treatment of MDS, but resistance to this agent is common. To determine the mechanisms underlying decitabine resistance, we measured the mRNA expression of metabolism (hENT1, DCK, CDA) and apoptosis (BCL2L10) genes and found that the hENT1 mRNA level was significantly higher in response compared with non-response patients (P=0.004). Furthermore, the DCK level was significantly reduced for relapse (P=0.012) compared with those with continued marrow CR (P=0.222). These findings indicate that the decitabine metabolic pathway affects its therapeutic effects, lower hENT1 expression may induce primary resistance and down-regulated DCK expression may be related to secondary resistance.
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Zesheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China. Electronic address: miyadu@hotmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077209:Decitabine; D003842:Deoxycytidine Kinase / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D033721:Equilibrative Nucleoside Transporter 1 / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D004791:Enzyme Inhibitors; D033721:Equilibrative Nucleoside Transporter 1; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; D000077209:Decitabine; D003842:Deoxycytidine Kinase; D001374:Azacitidine
keywords: DCK gene; Decitabine; Resistance; hENT1 gene