{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:26:54Z","timestamp":1767338814570,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIMAGO\u2014Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal","award":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"],"award-info":[{"award-number":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"]}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"],"award-info":[{"award-number":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"COMPETE-FEDER","doi-asserted-by":"publisher","award":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"],"award-info":[{"award-number":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"],"award-info":[{"award-number":["Project 18\/12","UID\/NEU\/04539\/2013","UID\/NEU\/04539\/2019","PO-CI-01-0145-FEDER-007440","SFRH\/BD\/51994\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants\u2014SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters\u2019 SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.<\/jats:p>","DOI":"10.3390\/ijms23179815","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"9815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-6433","authenticated-orcid":false,"given":"Raquel","family":"Alves","sequence":"first","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-8077","authenticated-orcid":false,"given":"Joana","family":"Jorge","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}]},{"given":"Gilberto","family":"Marques","sequence":"additional","affiliation":[{"name":"Clinical Pathology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-2310","authenticated-orcid":false,"given":"Andr\u00e9 B.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"given":"Rita","family":"Tenreiro","sequence":"additional","affiliation":[{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3426-6363","authenticated-orcid":false,"given":"Margarida","family":"Coucelo","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"given":"Joana","family":"Diamond","sequence":"additional","affiliation":[{"name":"Hemato-Oncology Laboratory, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil EPE, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-8161","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Oliveiros","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Am\u00e9lia","family":"Pereira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Medicine Service, Hospital da Luz, 3020-479 Coimbra, Portugal"},{"name":"Medicine Department, Hospital Distrital da Figueira da Foz, EPE, 3094-001 Figueira da Foz, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7832-4134","authenticated-orcid":false,"given":"Paulo","family":"Freitas-Tavares","sequence":"additional","affiliation":[{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]},{"given":"Ant\u00f3nio M.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Hospital da Luz Lisboa, 1500-650 Lisbon, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sa\u00fade (CIIS), Faculdade de Medicina, Universidade Cat\u00f3lica Portuguesa de Lisboa, 2635-631 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-4841","authenticated-orcid":false,"given":"Ana Bela","family":"Sarmento-Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology (LOH), University Clinic of Hematology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"},{"name":"Hematology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-061 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1007\/s11095-017-2148-9","article-title":"Inter-Subject Variability in OCT1 Activity in 27 Batches of Cryopreserved Human Hepatocytes and Association with OCT1 mRNA Expression and Genotype","volume":"34","author":"Fattah","year":"2017","journal-title":"Pharm. 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