Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia
Author
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Farfán Urzúa, Mauricio Javier
Author
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Salas, Carolina
es_CL
Author
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Canales López, Cristina
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Author
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Silva, Felipe
es_CL
Author
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Villarroel, Milena
es_CL
Author
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Kopp, Katherine
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Author
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Torres Torretti, Juan Pablo
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Author
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Santolaya de Pablo, María Elena
es_CL
Author
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Morales, Jorge
es_CL
Admission date
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2014-12-17T20:25:02Z
Available date
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2014-12-17T20:25:02Z
Publication date
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2014
Cita de ítem
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Citacion: BMC Cancer 2014, 14:299
en_US
Identifier
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doi:10.1186/1471-2407-14-299
Identifier
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https://repositorio.uchile.cl/handle/2250/129420
General note
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Artículo de publicación ISI
en_US
Abstract
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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.
en_US
Patrocinador
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This work was supported by grants from Fundación Nuestros Hijos (JM and
MJF) and FONDECYT 1120809 (MJF). We are indebted to and pleased to
acknowledge Drs. Mary V. Relling and Cristine Crews for TPMT activity
measurement.