ArticleCancer research and treatment2018
NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia.
Article in Cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled 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
- Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Severe Thiopurine-Induced Myelosuppression in a Pediatric Acute Lymphoblastic Leukemia Patient With the NUDT15 *1/*6 Genotype: A Brief Report.Clinical and translational science · 2026Article
- Genetic Determinants of Hematopoietic Toxicity Risk in Thai Pediatric Patients Undergoing 6-Mercaptopurine Treatment.Clinical and translational science · 2026Article
- The evaluation of the impact of NUDT15 variants on thiopurine metabolism in Japanese children with acute lymphoblastic leukemia.Cancer chemotherapy and pharmacology · 2025Article
- The frequency ofFrontiers in oncology · 2024Article
- The influence ofHGG advances · 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
- Pharmacogenomics in Children.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- [Effect of genetic polymorphism of TPMT and NUDT15 on the tolerance of 6-mercaptopurine therapy in adult acute lymphoblastic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- The Effect ofChildren (Basel, Switzerland) · 2021Article
- Article
- Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study.Frontiers in pharmacology · 2021Article
- Precision therapy of 6-mercaptopurine in Chinese children with acute lymphoblastic leukaemia.British journal of clinical pharmacology · 2020Article
- Association ofGenes · 2020Article
- Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn's disease patients.World journal of gastroenterology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). MATERIALS AND
methodsGenotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated.
resultsA total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group.
conclusionNUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.
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