title: SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia.
abstract: OBJECTIVE
  The solute carrier family 29 (equilibrative nucleoside transporter), member 1 (SLC29A1) is known to be involved in the transportation and resistance of the nucleoside analog cytosine arabinoside (AraC), one of the most effective drugs in the treatment of acute myeloid leukemia (AML).
  
  
  METHODS
  In vitro functional analysis in AML cells and genetic association study were performed.
  
  
  RESULTS
  Our functional analysis of SLC29A1 on anticancer effects of AraC showed that cytotoxic effects of AraC in AML cell lines were decreased by the reduction of SLC29A1 expression (P < 0.05). To investigate whether SLC29A1 polymorphisms could affect the achievement of complete remission (CR) in AML, we genotyped a total of six common single nucleotide polymorphisms on SLC29A1 in 103 AML patients, including 17 successes and 86 failures in CR. As a result, rs3734703 in 3'-untranslated region was significantly associated with CR even after correction for multiple testing (Fisher's exact test, P = 0.008; P corr = 0.04). A haplotype, ht3 (A-G-G-T-C-A; frequency = 0.294 in success group; frequency = 0.120 in failure group), also revealed a significant association with CR (P = 0.01; simulated P sim = 0.02).
  
  
  CONCLUSIONS
  Although further replication in larger subjects and further functional evaluations are required, our results suggest the contribution of SLC29A1 to cytotoxic effects of AraC. In addition, genetic variations of SLC29A1 could be a potential marker for the achievement of CR of cancers of white blood cells including AML.
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Chansu
authors.initials: C
authors.lastname: Lee
authors.affiliation: Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Functional Genome Institute, PDXen Biosystem Inc., Seoul, Republic of Korea.
authors.forename: Kwang-Sung
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea.|Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea.|Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. ssysmc@snu.ac.kr.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. ssysmc@snu.ac.kr.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. ssysmc@snu.ac.kr.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology*; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003561:Cytarabine
keywords: Acute myeloid leukemia (AML); AraC; Remission; SLC29A1; Single nucleotide polymorphism