ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 100 citations in OpenAlex.
- Nudix hydrolase 15 deficiency and azathioprine toxicity in a liver transplant recipient: A case report.JPGN reports · 2026Article
- Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges.Current treatment options in oncology · 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
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Population frequencies of thiopurine-related pharmacogenes in healthy individuals from Kosovo.Human genome variation · 2026Article
- Review
- The NUDIX hydrolase NUDT5 regulates thiopurine metabolism and cytotoxicity.The Journal of clinical investigation · 2025Article
- Clinical Actionability of the NUDT15 *4 (p.R139H) Allele and Its Association With Hispanic Ethnicity.Clinical pharmacology and therapeutics · 2025Article
- Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.Inflammatory bowel diseases · 2024Article
- Genetic association analysis and frequency of NUDT15*3 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease in a large Dutch cohort.The pharmacogenomics journal · 2024Article
- Precision Medicine for Acute Lymphoblastic Leukemia in Children: A Review.Children (Basel, Switzerland) · 2024Review
- Biomarkers That Predict Crohn's Disease Outcomes.Journal of the Canadian Association of Gastroenterology · 2024Review
- Article
- Pharmacogenetics of 6-mercaptopurine in a black Zimbabwean cohort treated for acute lymphoblastic leukaemia.Pharmacogenomics · 2023Article
- The influence ofHGG advances · 2023Article
- 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
- Long-read HiFi sequencing of NUDT15: Phased full-gene haplotyping and pharmacogenomic allele discovery.Human mutation · 2022Article
- TPMT and NUDT15 Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase.The Journal of molecular diagnostics : JMD · 2022Review
- Characterization of Reference Materials for TPMT and NUDT15: A GeT-RM Collaborative Project.The Journal of molecular diagnostics : JMD · 2022Article
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeSevere hematotoxicity in patients with thiopurine therapy has been associated with genetic polymorphisms in the thiopurine S-methyltransferase (TPMT). While TPMT genetic testing is clinically implemented for dose individualization, alterations in the nudix hydrolase 15 (NUDT15) emerged as independent determinant of thiopurine-related hematotoxicity. Because data for European patients are limited, we investigated the relevance of NUDT15 in Europeans.
methodsAdditionally to TPMT phenotyping/genotyping, we performed in-depth Sanger sequencing analyses of NUDT15 coding region in 107 European patients who developed severe thiopurine-related hematotoxicity as extreme phenotype. Moreover, genotyping for NUDT15 variants in 689 acute lymphoblastic leukemia (ALL) patients was performed.
resultsAs expected TPMT was the main cause of severe hematotoxicity in 31% of patients, who were either TPMT deficient (10%) or heterozygous carriers of TPMT variants (21%). By comparison, NUDT15 genetic polymorphism was identified in 14 (13%) patients including one novel variant (p.Met1Ile). Six percent of patients with severe toxicity carried variants in both TPMT and NUDT15. Among patients who developed toxicity within 3 months of treatment, 13% were found to be carriers of NUDT15 variants.
conclusionTaken together, NUDT15 and TPMT genetics explain ~50% of severe thiopurine-related hematotoxicity, providing a compelling rationale for additional preemptive testing of NUDT15 genetics not only in Asians, but also in Europeans.
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