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Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib

2013-02Artigo científico Acesso aberto
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dc.contributor.authorGromicho, Marta
dc.contributor.authorMagalhães, Marta
dc.contributor.authorTorres, Fátima
dc.contributor.authorDinis, Joana
dc.contributor.authorFernandes, Alexandra R
dc.contributor.authorRendeiro, Paula
dc.contributor.authorTavares, Purificação
dc.contributor.authorLaires, António
dc.contributor.authorRueff, José
dc.contributor.authorRueff, Jose
dc.contributor.authorRodrigues, António S
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Investigação em Genética Molecular Humana (CIGMH)
dc.contributor.pblSpandidos Publications
dc.date.accessioned2023-11-21T22:03:10Z
dc.date.available2023-11-21T22:03:10Z
dc.date.issued2013-02
dc.description.abstractDespite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30\% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms. A relationship between the type of BCR-ABL1 transcript or ABCB1 or SLC22A1 genotype and response to treatment was not discovered. However, the studied genes had higher expression levels in follow-up compared to the diagnostic samples, demonstrating a possible induction in expression. IM-sensitive patients presented significantly higher values of SLC22A1 expression, suggesting higher drug influx. Most importantly, while responding patients demonstrated stable expression signatures in consecutive samples, there was considerable variation in IM-resistant patients, indicating that single point sampling expression signatures are not reliable in predicting clinical outcomes or prognostic features in these patients. Studies that assessed consecutive samples from CML patients in order to evaluate the variation in expression levels of transporter genes are limited yet our study emphasizes the importance of such approaches.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent10
dc.format.extent867746
dc.identifier.doi10.3892/or.2012.2153
dc.identifier.issn1021-335X
dc.identifier.otherPURE: 348895
dc.identifier.otherPURE UUID: b9f02a64-897b-4abc-b32a-0beef133f7d8
dc.identifier.otherresearchoutputwizard: 35491
dc.identifier.otherPubMed: 23229016
dc.identifier.otherWOS: 000313605100046
dc.identifier.otherScopus: 84872768729
dc.identifier.otherORCID: /0000-0003-2054-4438/work/89983974
dc.identifier.urihttp://hdl.handle.net/10362/160236
dc.language.isoeng
dc.peerreviewedyes
dc.subjectMOLECULAR RESPONSES
dc.subjectBCR-ABL1
dc.subjectABCG2
dc.subjectKINASE DOMAIN MUTATIONS
dc.subjectdrug resistance
dc.subjectMVP
dc.subjectFUSION GENE TRANSCRIPTS
dc.subjectSTANDARD-DOSE IMATINIB
dc.subjectEUROPEAN LEUKEMIANET
dc.subjecttyrosine kinase inhibitors
dc.subjectdrug transporters
dc.subjectSLC22A1
dc.subjectchronic myeloid leukemia
dc.subjectLOW OCT-1 ACTIVITY
dc.subjectSUBOPTIMAL RESPONSE
dc.subjectP-GLYCOPROTEIN
dc.subjectMULTIDRUG-RESISTANCE
dc.subjectABCC1
dc.subjectimatinib
dc.subjectABCB1
dc.subjectBINDING-CASSETTE TRANSPORTERS
dc.subjectABCB1
dc.subjectABCC1
dc.subjectABCG2
dc.subjectBCR-ABL1
dc.subjectChronic myeloid leukemia
dc.subjectDrug resistance
dc.subjectrug transporters
dc.subjectImatinib
dc.subjectMVP
dc.subjectSLC22A1
dc.subjectTyrosine kinase inhibitors
dc.titleInstability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatiniben
dc.typejournal article
degois.publication.firstPage741
degois.publication.issue2
degois.publication.lastPage750
degois.publication.titleOncology Reports
degois.publication.volume29
dspace.entity.typePublication
person.familyNameRueff
person.givenNameJose
person.identifier793666
person.identifier.ciencia-id0E15-908D-EA21
person.identifier.orcid0000-0002-8456-7295
person.identifier.ridE-6426-2013
person.identifier.scopus-author-id7006536439
rcaap.rightsopenAccess
relation.isAuthorOfPublication91a3b5ac-0328-498d-8cb8-08555b202306
relation.isAuthorOfPublication.latestForDiscovery91a3b5ac-0328-498d-8cb8-08555b202306

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