ReviewLeukemia2000
Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia.
Review in Leukemia, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00590941 (Candidate Gene Polymorphisms and Response to Rituximab-CHOP in Patients With Diffuse Large Cell Lymphoma), which is not on this map. Cited by 102 papers.
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.
Candidate Gene Polymorphisms and Response to Rituximab-CHOP in Patients With Diffuse Large Cell Lymphoma
Who cites it
102 citing papers in PubMed, 438 citations in OpenAlex.
- A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: the St Jude long-term follow-up.Bone marrow transplantation · 2012Trial
- Trial
- Association of Variants in Candidate Pharmacogenes with Response to Mercaptopurine and Methotrexate in Pediatric Acute Lymphoblastic Leukemia: A Single-Center Experience from Croatia.Oncology and therapy · 2026Article
- Reactive sulfur species are inactivated and excreted as trimethylsulfonium ion by thiopurine S-methyltransferase.Redox biology · 2026Article
- Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15.Human genomics · 2026Review
- The Environmental and Global Impact of Pharmacogenomics: Advancing Green Pharmacy Toward Sustainable and Inclusive Precision Medicine.Journal of personalized medicine · 2026Review
- Genetic Determinants of Hematopoietic Toxicity Risk in Thai Pediatric Patients Undergoing 6-Mercaptopurine Treatment.Clinical and translational science · 2026Article
- Impact of the loss of slc43a3 on 6-mercaptopurine absorption and tissue distribution in mice.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Clinical characteristics, diagnosis and management of Sweet syndrome induced by azathioprine.Clinical and experimental medicine · 2023Article
- Population-Specific Distribution ofTherapeutics and clinical risk management · 2023Article
- Technical Validation and Clinical Utility of an NGS Targeted Panel to Improve Molecular Characterization of Pediatric Acute Leukemia.Frontiers in molecular biosciences · 2022Article
- Pharmacogenomics in Children.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The application of "Omics" to accelerate precision medicine in Supportive Care in Cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Article
- NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells.Journal of cellular and molecular medicine · 2021Article
- Article
- Biomarkers for gastrointestinal adverse events related to thiopurine therapy.World journal of gastroenterology · 2021Article
- Genetic Polymorphisms in Pharmaceuticals and Chemotherapy.World journal of oncology · 2021Review
- Cost-effectiveness analysis of genotype screening and therapeutic drug monitoring in patients with inflammatory bowel disease treated with azathioprine therapy: a Chinese healthcare perspective using real-world data.Annals of translational medicine · 2021Article
- Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients.Journal of pediatric genetics · 2021Article
- Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.Vox sanguinis · 2021Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurines, including 6-mercaptopurine and 6-thioguanine. TPMT activity exhibits genetic polymorphism, with about 1/300 inheriting TPMT deficiency as an autosomal recessive trait. If treated with standard doses of thiopurines, TPMTdeficient patients accumulate excessive thioguanine nucleotides in hematopoietic tissues, leading to severe hematological toxicity that can be fatal. However, TPMT-deficient patients can be successfully treated with a 10- to 15-fold lower dosage of these medications. The molecular basis for altered TPMT activity has been defined, with rapid and inexpensive assays available for the three signature mutations which account for the majority of mutant alleles. TPMT genotype correlates well with in vivo enzyme activity within erythrocytes and leukemic blast cells and is clearly associated with risk of toxicity. The impact of 6-mercaptopurine dose intensity is also being clarified as an important determinate of event-free survival in childhood leukemia. In addition, there are emerging data that TPMT genotype may influence the risk of secondary malignancies, including brain tumors and acute myelogenous leukemia. Ongoing studies aim to clarify the influence of TPMT on thiopurine efficacy, acute toxicity, and risk for delayed toxicity. Together, these advances hold the promise of improving the safety and efficacy of thiopurine therapy.
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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.