Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

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

Mauricio J Farfan12*, Carolina Salas2, Cristina Canales1, Felipe Silva2, Milena Villarroel2, Katherine Kopp2, Juan P Torres2, María E Santolaya12 and Jorge Morales2

Author Affiliations

1 Departamento de Pediatría, Centro de Estudios Moleculares, Facultad de Medicina, Universidad de Chile, Antonio Varas 360, Santiago, Chile

2 Hospital Dr. Luis Calvo Mackenna, Santiago, Chile

For all author emails, please log on.

BMC Cancer 2014, 14:299  doi:10.1186/1471-2407-14-299

Published: 28 April 2014

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.

Keywords:
Genetic polymorphism; Acute lymphoblastic leukemia (ALL); 6-Mercaptopurine; TPMT