Thiopurine-S-Methyltransferase Gene Polymorphism and Drug-related Toxicity in Children Treated for Acute Leukemia and Non-Hodgkin’s Lymphoma

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dc.authorid260725en_US
dc.authorid162141en_US
dc.authorid56681en_US
dc.authorid1438en_US
dc.authorid31583en_US
dc.contributor.authorAktan, Çağdaş
dc.contributor.authorAtaseven, Eda
dc.contributor.authorKosova, Buket
dc.contributor.authorKurugöl, Zafer
dc.contributor.authorKantar, Mehmet
dc.date.accessioned2023-01-30T07:36:11Z
dc.date.available2023-01-30T07:36:11Z
dc.date.issued2022
dc.departmentİstanbul Beykent Üniversitesien_US
dc.description.abstractAim: Thiopurine S-methyltransferase (TPMT) is an essential enzyme in the metabolism of thiopurine drugs, and its activity may change due to different polymorphisms in the TPMT gene. The TPMT gene has different genetic polymorphisms in different ethnic groups. This study aimed to determine the frequency of TPMT polymorphisms in children with acute leukemia/non-Hodgkin lymphoma (AL/NHL) and healthy children and to evaluate their association with severe toxicities in the study population. Materials and Methods: Sixty-seven pediatric AL/NHL patients and 84 healthy children were evaluated. Genotyping for the TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*4, TPMT*5, TPMT*6, and TPMT*7 alleles were performed by the real-time polymerase chain reaction technique. The number of grade 3 or higher hematologic and hepatic toxicities were recorded from the patient charts. Results: In the AL/NHL patients, we found that the patients had generally wild-type TPMT*1 allele in 80.6%, whereas TPMT*2 (238G>C) was seen in 1.5%, TPMT*3A (c.460G>A and c.719A>G) in 0%, and TPMT*3B polymorphisms (460G>A) in 17.9%. We found wild-type TPMT*1 allele in 98.8% and TPMT*3B polymorphisms (460G>A) in 1.2% of the healthy volunteers. Grade ?3 myelosuppression developed in 22/54 patients with the wild type allele, and it developed in 5/12 patients with TPMT*3B allele. Six (8.9%) patients had grade ?3 aspartate aminotransferase elevations, 17 (25%) patients had grade ?3 alanine transaminase elevations (1-5 times), and 42 patients had (62.6%) grade ?3 total bilirubin elevations. Conclusion: TPMT*3B polymorphism was the most common allele detected in our study group. This allele frequency is very high in comparison to other studies from our country and it was over-represented in comparison to the healthy volunteers. We did not find any relationship between severe hematologic/hepatic toxicities and TPMT gene polymorphisms.en_US
dc.identifier.doi10.4274/jpr.galenos.2021.35492
dc.identifier.issn2147-9445
dc.identifier.trdizinid527473en_US
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/527473
dc.identifier.urihttps://doi.org/10.4274/jpr.galenos.2021.35492
dc.identifier.wosWOS:000766885300012en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakTR-Dizinen_US
dc.language.isoenen_US
dc.publisherGalenos Publishing Houseen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.subjectThiopurine S-methyltransferaseen_US
dc.subjectleukemiaen_US
dc.subjectlymphomaen_US
dc.subjectpolymorphismen_US
dc.subjecttoxicityen_US
dc.subjectchildhooden_US
dc.titleThiopurine-S-Methyltransferase Gene Polymorphism and Drug-related Toxicity in Children Treated for Acute Leukemia and Non-Hodgkin’s Lymphomaen_US
dc.typeArticleen_US

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