Unknown

Dataset Information

0

Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.


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.

SUBMITTER: Farfan MJ 

PROVIDER: S-EPMC4012712 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.

Farfan Mauricio J MJ   Salas Carolina C   Canales Cristina C   Silva Felipe F   Villarroel Milena M   Kopp Katherine K   Torres Juan P JP   Santolaya María E ME   Morales Jorge J  

BMC cancer 20140428


<h4>Background</h4>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.<h4>Methods</h4>103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated fr  ...[more]

Similar Datasets

| S-EPMC6718715 | biostudies-literature
| S-EPMC5932771 | biostudies-literature
| S-EPMC7998516 | biostudies-literature
| S-EPMC8400562 | biostudies-literature
| S-EPMC8518605 | biostudies-literature
| S-EPMC8763585 | biostudies-literature
| S-EPMC5587295 | biostudies-literature
| S-EPMC8702453 | biostudies-literature
| S-EPMC9027773 | biostudies-literature
| S-EPMC4375304 | biostudies-literature