ArticleLeukemia2020
UGT1A1 genotype influences clinical outcome in patients with intermediate-risk acute myeloid leukemia treated with cytarabine-based chemotherapy.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- [Interactions between common drug metabolism and precautions for drug usage in Gilbert syndrome].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study.Frontiers in oncology · 2024Article
- E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia.Annals of hematology · 2023Article
- The Roles of Drug Metabolism-Related ADH1B in Immune Regulation and Therapeutic Response of Ovarian Cancer.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
23 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The treatment of acute myeloid leukemia (AML) is adjusted according to cytogenetic risk factors and molecular markers. Cytarabine remains the main drug to treat AML, and several studies have explored the prognostic relevance of the genotype of cytarabine metabolizing enzymes in AML. Glucuronidation has been identified to be relevant in the cytarabine clearance, but there are still few data concerning the clinical impact of genetic polymorphisms known to condition the activity of UDP-glucuronosyl transferases in AML patients. Here we report the association between the UGT1A1 rs8175347 genotype and the clinical outcome of 455 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients with the UGT1A1*28 homozygous variant (associated to a lower UGT1A1 activity) had a lower overall survival (OS) (25.8% vs. 45.5%; p: 0.004). Multivariate analysis confirmed this association (p: 0.008; HR: 1.79; 95% CI: 1.16-2.76). Subgroup analysis showed the negative effect of the UGT1A1*28 homozygous genotype on OS in women (14.8% vs. 52.7%; p: 0.001) but not in men. This lower OS was associated with longer neutropenia after consolidation chemotherapy and with higher mortality without previous relapse, suggesting an association between a low glucuronidation activity and mortal toxic events.
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