PMID- 12043054
OWN - NLM
STAT- MEDLINE
DCOM- 20020813
LR  - 20080716
IS  - 0029-2001 (Print)
IS  - 0029-2001 (Linking)
VI  - 122
IP  - 11
DP  - 2002 Apr 30
TI  - [New techniques for optimization of thiopurine therapy in leukemia and 
      transplantation].
PG  - 1107-10
AB  - BACKGROUND: The majority of chemotherapeutic agents are administered at fixed 
      doses that are close to those maximally tolerated. MATERIAL AND METHODS: This 
      review is based on current knowledge about the metabolism of thiopurines and the 
      clinical implications of genetic polymorphism in thiopurine-S-methyltransferase 
      (TPMT). RESULTS: Intracellularly thiopurines, e.g. 6-MP, are anabolized to 
      cytotoxic 6-thioguanine nucleotides (6-TGN) that are incorporated into DNA and 
      RNA. A competing pathway is S-methylation of 6-MP and its initial nucleotide 
      metabolites by TPMT. In childhood acute lymphocytic leukaemia, high erythrocyte 
      concentrations of 6-TGN correlate with the degree of leukopenia and a good 
      prognosis, while low concentrations appear to be associated with higher risk of 
      relapse. In most populations studied, approximately 10% have intermediate TPMT 
      activity and 1/300 lacks TPMT activity due to one or two mutant TPMT alleles, 
      respectively. INTERPRETATION: Phenotyping or genotyping may be used to identify 
      patients as deficient or intermediate thiopurine metabolizers. This suggests that 
      they should receive a profound or moderate reduction in dosage to avoid 
      haematopoietic toxicity.
FAU - Loennechen, Thrina
AU  - Loennechen T
AD  - Avdeling for farmakologi Institutt for farmasi, Universitetet i Tromso 9037 
      Troms. thrinal@farmasi.uit.no
FAU - Lysaa, Roy Andre
AU  - Lysaa RA
FAU - Giverhaug, Trude
AU  - Giverhaug T
FAU - Sylte, Ingebrigt
AU  - Sylte I
FAU - Mathiesen, Lars-Eirik
AU  - Mathiesen LE
FAU - Aarbakke, Jarle
AU  - Aarbakke J
LA  - nor
PT  - English Abstract
PT  - Journal Article
PT  - Review
TT  - Nye styringsverktoy for tiopuriner i leukemi- og transplantasjonsbehandling.
PL  - Norway
TA  - Tidsskr Nor Laegeforen
JT  - Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny 
      raekke
JID - 0413423
RN  - 0 (Antimetabolites)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Purines)
RN  - EC 2.1.1.- (Methyltransferases)
SB  - IM
MH  - Adult
MH  - Antimetabolites/*administration & dosage/metabolism
MH  - Antimetabolites, Antineoplastic/*administration & dosage/metabolism
MH  - Child
MH  - Genotype
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/metabolism
MH  - Methyltransferases/genetics/metabolism
MH  - *Organ Transplantation
MH  - *Pharmacogenetics
MH  - Phenotype
MH  - Polymorphism, Genetic
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/genetics/metabolism
MH  - Purines/*administration & dosage/metabolism
RF  - 30
EDAT- 2002/06/05 10:00
MHDA- 2002/08/14 10:01
CRDT- 2002/06/05 10:00
PHST- 2002/06/05 10:00 [pubmed]
PHST- 2002/08/14 10:01 [medline]
PHST- 2002/06/05 10:00 [entrez]
PST - ppublish
SO  - Tidsskr Nor Laegeforen. 2002 Apr 30;122(11):1107-10.