ArticleLeukemia2024
The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.
Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Organic cation transporter novel 1 (OCTN1): beyond an ergothioneine transporter.Cell communication and signaling : CCS · 2026Review
- Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Article
- Influence of genetic variants of imatinib on pharmacokinetics and recurrence-free survival in postoperative patients with gastrointestinal stromal tumor.European journal of clinical pharmacology · 2025Article
- Treatment Cessation in Chronic Myeloid Leukemia: Evidence and Uncertainties.Hematological oncology · 2025Review
- The Human OCTN Sub-Family: Gene and Protein Structure, Expression, and Regulation.International journal of molecular sciences · 2024Review
- Molecular biomarkers of leukemia: convergence-based drug resistance mechanisms in chronic myeloid leukemia and myeloproliferative neoplasms.Frontiers in pharmacology · 2024Review
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Authors and funding
37 authors at 20 institutions in 7 countries.
Funding
Abstract
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
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