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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
K. Machova Polakova, A. Albeer, V. Polivkova, M. Krutska, K. Vlcanova, N. Curik, A. Fabarius, H. Klamova, B. Spiess, CF. Waller, TH. Brümmendorf, J. Dengler, V. Kunzmann, A. Burchert, P. Belohlavkova, S. Mustjoki, E. Faber, J. Mayer, D. Zackova,...
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
00023736
Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)
NCN 2018/31/B/NZ6/03361
Narodowe Centrum Nauki (National Science Centre)
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Nursing & Allied Health Database (ProQuest)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
- MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * drug therapy genetics MeSH
- Imatinib Mesylate therapeutic use MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Humans MeSH
- Membrane Transport Proteins therapeutic use MeSH
- Prognosis MeSH
- Antineoplastic Agents * adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Bergonie Institute Bordeaux Inserm U1218 University of Bordeaux Bordeaux France
Department of General Pathology Pomeranian Medical University Szczecin Poland
Department of Hematology Jagiellonian University Hospital Kraków Poland
Department of Hematology Medical University of Lodz Copernicus Memorial Hospital Lodz Poland
Department of Hematology St Olavs Hospital Trondheim Norway
Dept of Hematology Oncology and Radiation Physics Skåne University Hospital Lund Sweden
Experimental Hematooncology Department University of Lublin Lublin Poland
Hematology and Bone Marrow Transplantation Department Medical Silesian University Katowice Poland
Hematology and Transplantology Department Medical University of Gdańsk Gdańsk Poland
Hematology Clinic National and kapodistrian University Athens Greece
Hematology Department Medical University of Białystok Białystok Poland
Hematology Oncology and Internal Medicine Department Medical University of Warsaw Warsaw Poland
Institute of Hematology and Blood Transfusion Prague Czech Republic
Onkologische Praxis Heilbronn Heilbronn Germany
Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik 2 Würzburg Germany
References provided by Crossref.org
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