title: [Not Available].
abstract: 6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the active compounds and into methylated metabolites, primary by thiopurine S-methyltransferase enzyme (TPMT). This enzyme displays important inter subject variability linked to a genetic polymorphism: when treated with standard doses of thiopurine, TPMT-deficient and heterozygous patients are at great risk for developing severe and potentially life-threatening toxicity (hematopoietic, hepatic, mucositis. . . ) but show a better survival rate while patients with high TPMT activity (wild type) present lower peripheral red blood cells 6-TGN concentrations and a higher risk of leukemia relapse. Genotyping remains crucial before 6-MP administration at diagnosis to identify patients with homozygous mutant TPMT genotype and therefore prevent severe and life-threatening toxicity, and to individualize therapy according to TMPT genotype. Follow-up of ALL treatment should preferentially be based on repeated determinations of intracellular active metabolites (6-thioguanine nucleotides) and methylated metabolites in addition to haematological surveillance.
authors.affiliation: Laboratoire de Pharmacologie Pédiatrique et Pharmacogénétique, Hôpital Robert Debré, Paris, France.
authors.forename: May
authors.initials: M
authors.lastname: Fakhoury
authors.affiliation: Laboratoire de Pharmacologie Pédiatrique et Pharmacogénétique, Hôpital Robert Debré, Paris, France. Electronic address: evelyne.jacqz-aigrain@rdb.aphp.fr.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
authors.forename: Tiphaine
authors.initials: T
authors.lastname: de Beaumais
authors.forename: Yves
authors.initials: Y
authors.lastname: Médard
keywords: 6-mercaptopurine; TPMT; acute lymphoblastic leukaemia; leucémie aigue lymphoblastique; pediatry; pédiatrie