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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

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

Published: 28 April 2014



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.


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.


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.


TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.

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