title: TPMT gene expression is increased during maintenance therapy in childhood acute lymphoblastic leukemia patients in a TPMT gene promoter variable number of tandem repeat-dependent manner.
abstract: OBJECTIVE
  6-mercaptopurine influences in vitro TPMT gene expression in a TPMT promoter variable number of tandem repeats (VNTR)-dependent manner. We studied TPMT expression following 6-mercaptopurine and methotrexate administration in childhood acute lymphoblastic leukemia (ALL) patients and the pharmacogenomic potential of the VNTR architecture.
  
  
  METHODS
  TPMT gene expression was determined in childhood ALL patients at diagnosis (n = 57) and during the maintenance therapy (n = 27).
  
  
  RESULTS
  A threefold increase of TPMT gene expression was obtained during maintenance therapy, modulated by the architecture of the VNTR region.
  
  
  CONCLUSIONS
  The TPMT promoter genetic variants need to be considered at the very beginning of the maintenance therapy for childhood ALL patients. The TPMT promoter VNTR region may serve as a pharmacogenomic biomarker when introducing thiopurine therapy.
authors.affiliation: Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kotur
authors.affiliation: University Children's Hospital, School of Medicine, University of Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Dokmanovic
authors.affiliation: University Children's Hospital, School of Medicine, University of Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Janic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Stankovic
authors.affiliation: University Children's Hospital, School of Medicine, University of Belgrade, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Krstovski
authors.affiliation: Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosic
authors.affiliation: Department of Pharmacy, University of Patras, School of Health Sciences, Patras, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Katsila
authors.affiliation: Department of Pharmacy, University of Patras, School of Health Sciences, Patras, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.affiliation: Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Zukic
authors.affiliation: Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D060046:Maintenance Chemotherapy; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D008780:Methyltransferases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D018598:Minisatellite Repeats; D009000:Monocytes / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D008727:Methotrexate
keywords: 6-mercaptopurine; TPMT expression; TPMT genetic variations; VNTR; childhood acute lymphoblastic leukemia; maintenance therapy; pharmacogenomics; variable number of tandem repeats