Trial reportThe pharmacogenomics journal2017
Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia.
Trial report in The pharmacogenomics journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Ethnic Differences in the Association Between SOD2 rs4880 and Hepatotoxicity in Pediatric Acute Lymphoblastic Leukemia: A Report From the REDIAL Consortium.Pediatric blood & cancer · 2026Article
- Systematic review on genetic polymorphisms associated with idiosyncratic drug-induced liver injury (iDILI): iDILInet as an interactive visualization tool.Acta pharmaceutica Sinica. B · 2026Article
- The impact of asparaginase phenotype-related single nucleotide polymorphisms on prognosis in pediatric B-cell precursor acute lymphoblastic leukemia.European journal of medical research · 2025Article
- Pharmacogenomics Applied to Acute Leukemias: Identifying Clinically Relevant Genetic Variants.Biomedicines · 2025Review
- Evaluating Asparaginase Toxicity in Hispanic Patients With Acute Lymphoblastic Leukemia in a Large Safety-Net Hospital.World journal of oncology · 2025Article
- Article
- Hispanic ethnicity and the rs4880 variant in SOD2 are associated with elevated liver enzymes and bilirubin levels in children receiving asparaginase-containing chemotherapy for acute lymphoblastic leukemia.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods.International journal of molecular sciences · 2022Review
- Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.Frontiers in pediatrics · 2022Review
- Pharmacogenetics of induction therapy-related toxicities in childhood acute lymphoblastic leukemia patients treated with UKALL 2003 protocol.Scientific reports · 2021Article
- Genetic Diversity of Drug-Related Genes in Native Americans of the Brazilian Amazon.Pharmacogenomics and personalized medicine · 2021Article
- Pharmacogenomics and ALL treatment: How to optimize therapy.Seminars in hematology · 2020Review
- Efficacy and toxicity of reduced vs. standard dose pegylated asparaginase in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia.Leukemia & lymphoma · 2020Article
- The Metabolic Profiles in Hematological Malignancies.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2019Review
- Decoding the role of SOD2 in sickle cell disease.Blood advances · 2019Review
- L-carnitine does not ameliorate asparaginase-associated hepatotoxicity in a C57BL6 mouse model.Leukemia & lymphoma · 2019Article
- Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Levocarnitine for asparaginase-induced hepatic injury: a multi-institutional case series and review of the literature.Leukemia & lymphoma · 2018Review
- Predictors of hepatotoxicity and pancreatitis in children and adolescents with acute lymphoblastic leukemia treated according to contemporary regimens.Pediatric blood & cancer · 2018Article
- Asparaginase toxicity in Hispanic adult and pediatric patients with acute lymphoblastic leukemia: current understanding.Expert opinion on drug metabolism & toxicologyReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Asparaginase, which depletes asparagine and glutamine, activates amino-acid stress response. Oxidative stress mediated by excessive reactive oxygen species (ROS) causes enhanced mitochondrial permeabilization and subsequent cell apoptosis and is considered as a plausible mechanism for drug-induced hepatotoxicity, a common toxicity of asparaginase in adults with acute lymphoblastic leukemia (ALL). Studies investigating the pharmacogenetics of asparaginase in ALL are limited and focused on asparaginase-induced allergic reaction common in pediatric patients. Here, we sought to determine a potential association between the variant rs4880 in SOD2 gene, a key mitochondrial enzyme that protects cells against ROS, and hepatotoxicity during asparaginase-based therapy in 224 patients enrolled on CALGB-10102, a treatment trial for adults with ALL. We report that the CC genotype of rs4880 is associated with increased hepatotoxicity following asparaginase-based treatment. Thus, rs4880 likely contributes to asparaginase-induced hepatotoxicity, and functional studies investigating this single-nucleotide polymorphism (SNP) are needed to develop therapeutic approaches that mitigate this toxicity.
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