ArticleThe Journal of pharmacology and experimental therapeutics2011
Genetic variants in cytosolic 5'-nucleotidase II are associated with its expression and cytarabine sensitivity in HapMap cell lines and in patients with acute myeloid leukemia.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Chromosome 10q24.32 Variants Associate With Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.Journal of the American Heart Association · 2023Pooled it
- Pooled it
- Pharmacogenomic Score Effectively Personalizes Treatment of Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Pharmacogenomics, Race, and Treatment Outcome in Pediatric Acute Myeloid Leukemia.JAMA network open · 2024Trial
- SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study.Journal of experimental & clinical cancer research : CR · 2014Trial
- Effect of NME2 and SAMHD1 genetic polymorphisms involved in Ara-C metabolism on the response to induction chemotherapy in adult acute myeloid leukemia.Journal of the Egyptian National Cancer Institute · 2025Article
- SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia.Blood advances · 2023Article
- Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.medRxiv : the preprint server for health sciences · 2023Article
- Role of Pharmacogenetics in the Treatment of Acute Myeloid Leukemia: Systematic Review and Future Perspectives.Pharmaceutics · 2022Review
- Polygenic Ara-C Response Score Identifies Pediatric Patients With Acute Myeloid Leukemia in Need of Chemotherapy Augmentation.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Whole genome, exon mutation and transcriptomic profiling of acute myeloid leukemia: A case report.Oncology letters · 2021Article
- Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers.Cancers · 2021Review
- Cellular Metabolomics Profiles Associated With Drug Chemosensitivity in AML.Frontiers in oncology · 2021Article
- A personalized approach to acute myeloid leukemia therapy: current options.Pharmacogenomics and personalized medicine · 2019Article
- Article
- Genome-wide association analysis identifies SNPs predictive ofOncotarget · 2018Article
- Comprehensive Ara-C SNP score predicts leukemic cell intracellular ara-CTP levels in pediatric acute myeloid leukemia patients.Pharmacogenomics · 2018Article
- Review
- 5'-nucleotidase cN-II emerges as a new predictive biomarker of response to gemcitabine/platinum combination chemotherapy in non-small cell lung cancer.Oncotarget · 2018Article
- Polymorphisms at microRNA binding sites of Ara-C and anthracyclines-metabolic pathway genes are associated with outcome of acute myeloid leukemia patients.Journal of translational medicine · 2017Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Cytosolic 5'-nucleotidase II (NT5C2) is involved in the development of 1-β-d-arabinofuranosylcytosine (ara-C) resistance and has been associated with clinical outcome in patients receiving ara-C-based chemotherapy. NT5C2 inactivates ara-C by dephosphorylating ara-C monophosphate to ara-C. In this study, we sequenced NT5C2 in genomic DNA samples from International HapMap project panels with European [Centre d'Etude du Polymorphisme Humain (CEU); n = 90] or African [Yoruba people in Ibadan, Nigeria (YRI); n = 90] ancestry. We identified 41 genetic variants [one insertion-deletion and 40 single nucleotide polymorphisms (SNPs)], including three nonsynonymous SNPs (Y3A, K47R, and Q136R). Twenty-five SNPs were novel and 16 overlapped with the HapMap data. Subjects with African ancestry had NT5C2 mRNA expression levels that was significantly higher than those with European ancestry (p = 0.005). Furthermore, there was a correlation between NT5C2 mRNA expression and ara-C sensitivity in CEU but not in YRI cell lines. None of the nonsynonymous SNPs demonstrated any effect on NT5C2 activity. The genotypes of several SNPs were significantly associated with NT5C2 mRNA expression and/or ara-C sensitivity in CEU cell lines, but very few were significant in YRI cell lines. Of most interest, SNPs (linkage disequilibrium group CEU.12) in the 5'-untranslated region were associated with NT5C2 expression and ara-C sensitivity in HapMap cell lines and with NT5C2 mRNA expression and ara-C sensitivity in diagnostic leukemic blasts from pediatric patients with acute myeloid leukemia. Functional genomics analysis demonstrated that the promoter SNP rs11191612 was associated with altered luciferase activation in reporter assays and altered DNA-protein binding in gel shift assays. These results suggest that genetic variations in NT5C2 influence its expression and, potentially, cellular responses to nucleoside analogs.
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Registered trials
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