ArticleJournal of experimental & clinical cancer research : CR2017
Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response of chronic myeloid leukemia patients to imatinib treatment.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Trial
- Organic cation transporter novel 1 (OCTN1): beyond an ergothioneine transporter.Cell communication and signaling : CCS · 2026Review
- Carnitine dysregulation in diabetic kidney disease: from pathogenic mechanism to precision biomarker.Journal of translational medicine · 2026Review
- The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers.International journal of molecular sciences · 2025Review
- Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia.Cancer research · 2025Article
- Contribution of genetic polymorphism inJournal of gastrointestinal oncology · 2024Article
- Inflammation and Organic Cation Transporters Novel (OCTNs).Biomolecules · 2024Review
- Article
- The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2023Review
- Clinical Significance of Carnitine in the Treatment of Cancer: From Traffic to the Regulation.Oxidative medicine and cellular longevity · 2023Review
- Targeting SOS1 overcomes imatinib resistance with BCR-ABL independence through uptake transporter SLC22A4 in CML.Molecular therapy oncolytics · 2021Article
- Review
- Carnitine Traffic in Cells. Link With Cancer.Frontiers in cell and developmental biology · 2020Review
- The argument for using imatinib in CML.Hematology. American Society of Hematology. Education Program · 2018Review
- AFLP-AFLP in silico-NGS approach reveals polymorphisms in repetitive elements in the malignant genome.PloS one · 2018Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThrough high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia.
methodsIn silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes. We analyzed cumulative achievement of major molecular response and probability of event free survival in relation to identified SNP genotypes in 129 CML patients and performed multivariate analysis for determination of genotypes as independent predictors of outcome. Gene expression analysis of eight cell lines naturally carrying different genotypes was performed to outline an impact of genotypes on the gene expression.
resultsWe observed significant differences in the frequencies of the rs460089-GC and rs460089-GG (SLC22A4) genotypes among rs2631365-TC (SLC22A5) genotype carriers that were associated with optimal and non-optimal responses, respectively. Loci rs460089 and rs2631365 were in highly significant linkage disequilibrium with 12 regulatory loci in introns of SLC22A4 and SLC22A5 encoding imatinib transporters. Genotype association analysis with the response to imatinib indicated that rs460089-GC carriers had a significantly higher probability of achieving a stable major molecular response (BCR-ABL1 transcript level below or equal to 0.1% in the international scale). In contrast, the rs460089-GG represented a risk factor for imatinib failure, which was significantly higher in rs460089-GG_rs2631365-TC carriers.
conclusionsThis exploratory study depicted potentially important genetic markers predicting outcome of imatinib treatment, which may be helpful for tailoring therapy in clinical practice.
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