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Genetic variants of ABC and SLC transporter genes and chronic myeloid leukaemia: impact on susceptibility and prognosis

2022-08-29Journal article Open access
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dc.contributor.authorAlves, Raquel
dc.contributor.authorGoncalves, Ana Cristina
dc.contributor.authorJorge, Joana
dc.contributor.authorMarques, Gilberto
dc.contributor.authorRibeiro, AndrƩ B.
dc.contributor.authorTenreiro, Rita
dc.contributor.authorCoucelo, Margarida
dc.contributor.authorDiamond, Joana
dc.contributor.authorOliveiros, BƔrbara
dc.contributor.authorPereira, AmƩlia
dc.contributor.authorFreitas-Tavares, Paulo
dc.contributor.authorAlmeida, AntĆ³nio M.
dc.contributor.authorSarmento-Ribeiro, Ana Bela
dc.date.accessioned2022-09-16T09:21:19Z
dc.date.available2022-09-16T09:21:19Z
dc.date.issued2022-08-29
dc.description.abstractSolute 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 variantsā€”SNVs) 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 transportersā€™ 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/ijms23179815pt_PT
dc.identifier.eid85137589835
dc.identifier.issn1661-6596
dc.identifier.pmcPMC9456284
dc.identifier.pmid36077209
dc.identifier.urihttp://hdl.handle.net/10400.14/38912
dc.identifier.wos000851202400001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCMLpt_PT
dc.subjectCancer predispositionpt_PT
dc.subjectTKI resistancept_PT
dc.subjectDrug transporterspt_PT
dc.titleGenetic variants of ABC and SLC transporter genes and chronic myeloid leukaemia: impact on susceptibility and prognosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue17pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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