ArticlePharmacogenomics2015
RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.
Article in Pharmacogenomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Chromosomal Heterogeneity and Enrichment of Mitotic Regulatory Programs Reveal a Therapeutic Vulnerability in Cytarabine-Resistant FLT3-ITD AML.Current issues in molecular biology · 2026Article
- Antileukemic Potential of Sodium Caseinate in Cytarabine-Resistant HL60-CR50 Human Leukemia Cells.Molecules (Basel, Switzerland) · 2025Article
- Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025Review
- Sodium Caseinate Induces Apoptosis in Cytarabine-Resistant AML by Modulating SIRT1 and Chemoresistance Genes, Alone or in Combination with Cytarabine or Daunorubicin.International journal of molecular sciences · 2025Article
- Antineoplastic Activity of Sodium Caseinate in a Cytarabine-Resistant Mouse Acute Myeloid Leukemia Cell Line.Nutrients · 2024Article
- 8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment.Biomolecules · 2023Article
- Posttranslational splicing modifications as a key mechanism in cytarabine resistance in acute myeloid leukemia.Leukemia · 2023Article
- Article
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Neurotoxicity Associated with Treatment of Acute Lymphoblastic Leukemia Chemotherapy and Immunotherapy.International journal of molecular sciences · 2022Review
- Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells.International journal of molecular sciences · 2021Article
- A novel upregulated LncRNA-AC026150.8 promotes chemo-resistance and predicts poor prognosis in acute myeloid leukemia.Cancer medicine · 2021Article
- Targeting IFN-γ-inducible lysosomal thiol reductase overcomes chemoresistance in AML through regulating the ROS-mediated mitochondrial damage.Translational oncology · 2021Article
- Optimal dosing of cytarabine in induction and post-remission therapy of acute myeloid leukemia.Leukemia · 2021Article
- Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance.Cancer cell international · 2021Article
- Downregulation of GLI3 Expression Mediates Chemotherapy Resistance in Acute Myeloid Leukemia.International journal of molecular sciences · 2020Article
- Identification of predictive genetic signatures of Cytarabine responsiveness using a 3D acute myeloid leukaemia model.Journal of cellular and molecular medicine · 2019Article
- Surmounting Cytarabine-resistance in acute myeloblastic leukemia cells and specimens with a synergistic combination of hydroxyurea and azidothymidine.Cell death & disease · 2019Article
- Evaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol.Systematic reviews · 2019Article
- A personalized approach to acute myeloid leukemia therapy: current options.Pharmacogenomics and personalized medicine · 2019Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundVariation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation.
methodsEx vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples.
resultsWide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples.
conclusionThis study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as treatment outcome. RI could be a predictor of ex vivo Ara-C response irrespective of cytogenetic and molecular risk groups and a potential biomarker for AML treatment outcome and toxicity. Original submitted 22 December 2014; Revision submitted 9 April 2015.
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