ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 60 citations in OpenAlex.
- Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia.The pharmacogenomics journal · 2016Trial
- Pharmacogenetic Predictors of Chemotherapy Treatment-Related Toxicities in Paediatric and Adolescent Acute Lymphoblastic Leukemia: A Systematic Review, Meta-Analysis and Literature-Based Candidate Prioritization.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A lipid-immune network signature defines susceptibility to asparaginase-associated pancreatitis.JCI insight · 2026Article
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Retrospective analysis of asparaginase-associated pancreatitis in pediatric acute lymphoblastic leukemia: focus on rechallenge with pegaspargase.Journal of cancer research and clinical oncology · 2025Review
- From Drug Discovery to Drug Approval: A Comprehensive Review of the Pharmacogenomics Status Quo with a Special Focus on Egypt.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A Review of L-Asparaginase Hypersensitivity in Paediatric Acute Lymphoblastic Leukaemia Patients with Regard to the Measurement of Anti-Asparaginase Antibodies and Their Genetic Predisposition.The Malaysian journal of medical sciences : MJMS · 2023Review
- A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis.Science translational medicine · 2023Article
- Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs.Frontiers in pharmacology · 2023Article
- Article
- Insights into Asparaginase from Endophytic FungusInternational journal of environmental research and public health · 2022Article
- Asparaginase-Associated Pancreatitis in Pediatric Patients with Acute Lymphoblastic Leukemia: Current Perspectives.Paediatric drugs · 2021Review
- Influence of genetic variants in asparaginase pathway on the susceptibility to asparaginase-related toxicity and patients' outcome in childhood acute lymphoblastic leukemia.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacogenomics and ALL treatment: How to optimize therapy.Seminars in hematology · 2020Review
- HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium.Pharmacogenomics · 2020Article
- Asparagine Synthetase Is Highly Expressed at Baseline in the Pancreas Through Heightened PERK Signaling.Cellular and molecular gastroenterology and hepatology · 2020Article
- Age modulates liver responses to asparaginase-induced amino acid stress in mice.The Journal of biological chemistry · 2019Article
- Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity.Pharmacology & therapeutics · 2019Review
- Review
- Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2019Review
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeAsparaginase (ASNase) is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia (ALL), but it is also associated with several toxicities. EXPERIMENTAL
designWe recently reported the results of an association study between ASNase pathway genes and event-free survival (EFS) in childhood patients with ALL. The same polymorphisms were interrogated here in relation to allergies, pancreatitis, and thrombotic events following treatment with E. coli ASNase.
resultsAmong patients of the discovery group, allergies, and pancreatitis were more frequent in individuals who are homozygous for the triple-repeat allele (3R) of the asparagine synthetase (ASNS) gene, resulting in remarkably higher risk of these toxicities associated with 3R3R genotype [OR for allergies, 14.6; 95% confidence interval (CI), 3.6-58.7; P < 0.0005 and OR for pancreatitis, 8.6; 95% CI, 2.0-37.3; P = 0.01]. In contrast, the ASNS haplotype *1 harboring double-repeat (2R) allele had protective effect against these adverse reactions (P ≤ 0.01). The same haplotype was previously reported to confer reduction in EFS. The risk effect of 3R3R genotype was not replicated in the validation cohort, whereas the protective effect of haplotype *1 against allergies was maintained (P ≤ 0.002). Analysis with additional polymorphisms in ASNS locus in lymphoblastoid cell lines showed that haplotype *1 is diversified in several subtypes of which one was associated with reduced in vitro sensitivity to ASNase (rs10486009, P = 0.01) possibly explaining an association seen in clinical setting.
conclusionsThis finding might have implication for treatment individualization in ALL and other cancers using asparagine depletion strategies. Clin Cancer Res; 21(2); 329-34. ©2014 AACR. See related commentary by Avramis, p. 230.
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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.