ArticleBMC cancer2018
Optimal predictor for 6-mercaptopurine intolerance in Chinese children with acute lymphoblastic leukemia: NUDT15, TPMT, or ITPA genetic variants?
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Association ofHaematologica · 2024Pooled it
- DNA-thioguanine nucleotide as a treatment marker in acute lymphoblastic leukemia patients with NUDT15 variant genotypes.PloS one · 2021Trial
- Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges.Current treatment options in oncology · 2026Review
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pharmacogenomics of Thiopurine Drugs: A Bench-To-Bedside Success Story in Thailand.Clinical and translational science · 2026Review
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Pharmacogenomics Applied to Acute Leukemias: Identifying Clinically Relevant Genetic Variants.Biomedicines · 2025Review
- Review
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Knowledge, attitude, and practice toward family-based treatment among parents of children with leukemia.Frontiers in public health · 2024Article
- The frequency ofFrontiers in oncology · 2024Article
- Pharmacogenetics of 6-mercaptopurine in a black Zimbabwean cohort treated for acute lymphoblastic leukaemia.Pharmacogenomics · 2023Article
- Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.Translational pediatrics · 2023Article
- Article
- Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia.Frontiers in pharmacology · 2023Article
- A direct sequencing assay for pharmacogenetic testing of thiopurine-intolerant NUDT15 alleles in an Asian population.BMC research notes · 2022Article
- NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China.International journal of hematology · 2022Article
- Article
- Article
- Pharmacogenomics in Children.Methods in molecular biology (Clifton, N.J.) · 2022Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
background6-mercaptopurine (6-MP) contributes substantially to remarkable improvement in the survival of childhood acute lymphoblastic leukemia (ALL) patients. However, 6-MP also has dose-limiting toxicities, particularly life-threatening myelosuppression, due to genetic polymorphisms in enzymes that metabolize 6-MP. Promising biomarkers for predicting 6-MP-induced leukopenia is still unclear in Chinese population. Here, we evaluated the associations of NUDT15, TPMT and ITPA genotypes with 6-MP intolerance in our cohort of childhood ALL patients.
methodsA total of 105 Chinese pediatric patients with a confirmed diagnosis of ALL were enrolled. We identified the NUDT15 coding variant rs116855232 (c.415C > T), a newly discovered 6-MP toxicity-related locus in Asians, and polymorphisms in TPMT rs1142345 and ITPA rs11273540. Associations between genotypes and 6-MP dose sensitivity, leukopenia, hepatotoxicity, and therapy interruption were evaluated.
resultsThe minor allele frequencies (MAFs) of NUDT15 rs116855232, TPMT rs1142345 and ITPA rs11273540 were 15.7, 2.9, and 18.1%, respectively. NUDT15 and TPMT genetic variants were strongly associated with 6-MP dose intensity. Patients with NUDT15 homogenous genotype (TT) were highly sensitive to 6-MP (dose intensity of 60.27%) compared to these with heterozygous genotype (TC) or wild type (CC), who tolerated an average dose intensity of 83.83 and 94.24%, respectively. The NUDT15 variant was a predictor for leukopenia (OR: 3.62, 95% CI 1.377-9.501, P = 0.009) and early-onset leukopenia (OR: 9.63, 95% CI 2.764-33.514, P = 3.75 × 10
conclusionNUDT15 variant is an optimal predictor for 6-MP intolerance in Chinese pediatric ALL patients and may have greatly clinical implications for individualized therapy.
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