Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.
BMC Cancer
; 14: 299, 2014 Apr 28.
Article
em En
| MEDLINE
| ID: mdl-24774509
ABSTRACT
BACKGROUND:
Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL.METHODS:
103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay.RESULTS:
The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles.CONCLUSION:
TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirofosfatases
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Mercaptopurina
/
Metiltransferases
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
America do sul
/
Chile
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article