dc.creator | Farfán Urzúa, Mauricio Javier | |
dc.creator | Salas, Carolina | |
dc.creator | Canales López, Cristina | |
dc.creator | Silva, Felipe | |
dc.creator | Villarroel, Milena | |
dc.creator | Kopp, Katherine | |
dc.creator | Torres Torretti, Juan Pablo | |
dc.creator | Santolaya de Pablo, María Elena | |
dc.creator | Morales, Jorge | |
dc.date.accessioned | 2014-12-17T20:25:02Z | |
dc.date.available | 2014-12-17T20:25:02Z | |
dc.date.created | 2014-12-17T20:25:02Z | |
dc.date.issued | 2014 | |
dc.identifier | Citacion: BMC Cancer 2014, 14:299 | |
dc.identifier | doi:10.1186/1471-2407-14-299 | |
dc.identifier | http://repositorio.uchile.cl/handle/2250/129420 | |
dc.description.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. | |
dc.language | en | |
dc.publisher | BioMed Central | |
dc.rights | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
dc.subject | Genetic polymorphism | |
dc.title | Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia | |
dc.type | Artículos de revistas | |