ArticleJournal of medical biochemistry2018
Variants in TPMT, ITPA, ABCC4 and ABCB1 Genes As Predictors of 6-mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia.
Article in Journal of medical biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Pharmacogenomics of Thiopurine Drugs: A Bench-To-Bedside Success Story in Thailand.Clinical and translational science · 2026Review
- Influence of xanthine oxidase and inosine monophosphate dehydrogenase polymorphisms on 6-mercaptopurine treatment response in pediatric acute lymphoblastic leukemia.Scientific reports · 2025Article
- Gene polymorphisms associated with immunosuppressant adverse effects in systemic lupus erythematosus: a narrative review.Frontiers in genetics · 2025Review
- Comprehensive pharmacogenomics profiling of the Serbian population.Frontiers in pharmacology · 2025Article
- Overcoming flumatinib resistance in chronic myeloid leukaemia: Insights into cellular mechanisms and ivermectin's therapeutic potential.Journal of cellular and molecular medicine · 2024Article
- DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?The pharmacogenomics journal · 2023Article
- Can Pharmacogenetic Variants inInternational journal of molecular sciences · 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
- PredictingACS omega · 2022Article
- A Systematic Review of Polygenic Models for Predicting Drug Outcomes.Journal of personalized medicine · 2022Review
- Effect of ITPA Polymorphism on Adverse Drug Reactions of 6-Mercaptopurine in Pediatric Patients with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The Effect ofChildren (Basel, Switzerland) · 2021Article
- Effects ofFrontiers in pediatrics · 2021Article
- Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations.Journal of medical biochemistry · 2020Article
- Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia.Journal of medical biochemistry · 2020Article
- Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology.Frontiers in pharmacology · 2020Review
- Implementation of Pharmacogenetics to Individualize Treatment Regimens for Children with Acute Lymphoblastic Leukemia.Pharmacogenomics and personalized medicine · 2020Review
- Expression Pattern of Long Non-coding RNA Growth Arrest-specific 5 in the Remission Induction Therapy in Childhood Acute Lymphoblastic Leukemia.Journal of medical biochemistry · 2019Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, and a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in the maintenance phase of treatment for children with acute lymphoblastic leukemia. For those patients, TPMT genotype- tailored 6-mercaptopurine therapy is already implemented in the treatment protocols. We investigated the role of TPMT, ITPA, ABCC4 and ABCB1 genetic variants as predictors of outcome and 6-mercaptopurine induced toxicity during the maintenance phase of treatment in pediatric acute lymphoblastic leukemia.
methodsSixty-eight children with acute lymphoblastic leukemia were enrolled in this study. Patients have been treated according to ALL IC-BFM 2002 or ALL IC-BFM 2009 protocols. Toxicity and adverse events have been monitored via surrogate markers (off-therapy weeks, episodes of leu - ko penia and average 6-mercaptopurine dose) and a prob- abilistic model was employed to predict overall 6-mercaptopurine related toxicity.
resultsWe confirmed that patients with acute lymphoblastic leukemia that carry inactive TPMT allele(s) require 6- mercaptopurine dose reduction. ITPA and ABCC4 genetic variants failed to show an association with 6-mercapto - purine induced toxicity during the maintenance phase. Carriers of ABCB1 variant allele experienced greater hepatotoxicity. The probabilistic model Neural net which considered all the analysed genetic variants was assessed to be the best prediction model. It was able to discriminate ALL patients with good and poor 6-mercaptopurin tolerance in 71% of cases (AUC=0.71).
conclusionsThis study contributes to the design of a panel of pharmacogenetic markers for predicting thiopurineinduced toxicity in pediatric ALL.
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