PMID- 22421815
OWN - NLM
STAT- MEDLINE
DCOM- 20121226
LR  - 20211021
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 68
IP  - 9
DP  - 2012 Sep
TI  - Pharmacogenetic determinants of mercaptopurine disposition in children with acute 
      lymphoblastic leukemia.
PG  - 1233-42
LID - 10.1007/s00228-012-1251-4 [doi]
AB  - BACKGROUND: The backbone of drug therapy used in acute lymphoblastic leukemia 
      (ALL) in children includes 6-mercaptopurine (6-MP). Intracellular metabolism of 
      this prodrug is a key component of the therapeutic response. Many metabolizing 
      enzymes are involved in 6-MP disposition and active 6-MP metabolites are 
      represented by 6-thioguanine nucleotides (6-TGN) and methylated metabolites 
      primarily methylated by the thiopurine S-methyltransferase enzyme (TPMT). The 
      genetic polymorphism affecting TPMT activity displays an important inter-subject 
      variability in metabolites pharmacokinetics and influences the balance between 
      6-MP efficacy and toxicity: patients with high 6-TGN levels are at risk of 
      myelosuppression while patients with high levels of methylated derivates are at 
      hepatotoxic risk. However, the genetic TPMT polymorphism does not explain all 
      6-MP adverse events and some severe toxicities leading to life-threatening 
      conditions remain unexplained. Additional single nucleotide polymorphisms (SNPs) 
      in genes encoding enzymes involved in 6-MP metabolism and 6-MP transporters may 
      also be responsible for this inter-individual 6-MP response variability. AIM: 
      This review presents the pharmacogenetic aspects of 6-MP metabolism in great 
      detail. We have focused on published data on ALL treatment supporting the great 
      potential of 6-MP pharmacogenetics to improve efficacy, tolerance, and event-free 
      survival rates in children with ALL.
FAU - Adam de Beaumais, Tiphaine
AU  - Adam de Beaumais T
AD  - Department of Pediatric Pharmacology and Pharmacogenetics, Robert Debre Hospital, 
      48 Boulevard Serurier, 75019 Paris, France. tiphaine.debeaumais@rdb.aphp.fr
FAU - Jacqz-Aigrain, Evelyne
AU  - Jacqz-Aigrain E
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20120316
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - E7WED276I5 (Mercaptopurine)
SB  - IM
MH  - Age Factors
MH  - Antimetabolites, Antineoplastic/adverse effects/*pharmacokinetics
MH  - Biotransformation/genetics
MH  - Child
MH  - Genotype
MH  - Humans
MH  - Mercaptopurine/adverse effects/*pharmacokinetics
MH  - *Pharmacogenetics
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/metabolism
EDAT- 2012/03/17 06:00
MHDA- 2012/12/27 06:00
CRDT- 2012/03/17 06:00
PHST- 2011/10/28 00:00 [received]
PHST- 2012/02/14 00:00 [accepted]
PHST- 2012/03/17 06:00 [entrez]
PHST- 2012/03/17 06:00 [pubmed]
PHST- 2012/12/27 06:00 [medline]
AID - 10.1007/s00228-012-1251-4 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2012 Sep;68(9):1233-42. doi: 10.1007/s00228-012-1251-4. 
      Epub 2012 Mar 16.