SynthesisOncotarget2017
Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose.
Synthesis in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Association of ITPA gene polymorphisms with adverse effects of AZA/6-MP administration: a systematic review and meta-analysis.The pharmacogenomics journal · 2022Pooled it
- Association between the c.415C > T, c.52G > A, and 36_37insGGAGTC polymorphisms ofDrug design, development and therapy · 2019Pooled it
- Pharmacogenomic variation and chemotherapy-related toxicity profiles in pediatric patients with cancer in Tanzania: a cross-sectional study.Frontiers in pharmacology · 2026Article
- 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
- Uphill battle: Innovation of thiopurine therapy in global inflammatory bowel disease care.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2024Review
- The frequency ofFrontiers in oncology · 2024Article
- 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
- Review
- TPMT and NUDT15 Variants Predict Discontinuation of Azathioprine for Myelotoxicity in Patients with Inflammatory Disease: Real-World Clinical Results.Clinical pharmacology and therapeutics · 2022Article
- Promising genes and variants to reduce chemotherapy adverse effects in acute lymphoblastic leukemia.Translational oncology · 2021Review
- Article
- Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine.Clinical rheumatology · 2021Review
- Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy.Cancer science · 2020Review
- Biomarkers Predictive of Response to Thiopurine Therapy in Inflammatory Bowel Disease.Frontiers in medicine · 2020Review
- Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia.Pharmacogenomics and personalized medicine · 2020Review
- Screening of Novel Pharmacogenetic Candidates for Mercaptopurine-Induced Toxicity in Patients With Acute Lymphoblastic Leukemia.Frontiers in pharmacology · 2020Article
- Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report.Experimental and therapeutic medicine · 2019Article
- Pharmacogenetics of thiopurines.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiopurines are widely used as anticancer and immunosuppressive agents. However, life-threatening myelotoxicity has been noticed and largely explained by genetic variations, including NUDT15 polymorphisms (e.g., rs116855232). In this study, we conduct a meta-analysis to investigate the impact of rs116855232 on thiopurines-induced myelotoxicity susceptibility (1752 patients from 7 independent cohorts), as well as on thiopurines intolerance dose (2745 patients from 13 cohorts). Variant allele of rs116855232 contributes 7.86-fold (P < 0.00001, 95% CI: 6.13-10.08) higher risk to develop leucopenia with high specificity (91.74%) and sensitivity (43.19%), and lower thiopurines intolerance dose (P < 0.00001). Through bioinformatics prediction, amino acid changes induced by genetic variants are considered to reduce the stability, and break an α helix of NUDT15, which is part of the thiopurine binding pocket. Additionally, we conduct an expression quantitative trait loci (eQTL) analysis for NUDT15, and find a promoter-located eQTL signal (rs554405994), which may act as a potential marker to predict thiopurines-induced myelotoxicity. In conclusion, genetic polymorphisms in NUDT15 are strongly associated with adverse drug reaction (ADR) of thiopurines, although more evidences are needed to determine values of all functional NUDT15 polymorphisms for clinical regimen, rs116855232 should be considered as a highly credible pharmacogenetic indicator for thiopurines using espcially is Asians.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.