Show simple item record

dc.contributor.authorOnecha, Esther
dc.contributor.authorLinares, Maria
dc.contributor.authorRapado, Inmaculada
dc.contributor.authorRuiz-Heredia, Yanira
dc.contributor.authorMartinez-Sanchez, Pilar
dc.contributor.authorCedena, Teresa
dc.contributor.authorPratcorona, Marta
dc.contributor.authorOteyza, Jaime Perez
dc.contributor.authorHerrera, Pilar
dc.contributor.authorBarragan, Eva
dc.contributor.authorMontesinos, Pau
dc.contributor.authorVela, Jose Antonio Garcia
dc.contributor.authorMagro, Elena
dc.contributor.authorAnguita, Eduardo
dc.contributor.authorFiguera, Angela
dc.contributor.authorRiaza, Rosalia
dc.contributor.authorMartinez-Barranco, Pilar
dc.contributor.authorSanchez-Vega, Beatriz
dc.contributor.authorNomdedeu, Josep
dc.contributor.authorGallardo, Miguel
dc.contributor.authorMartinez-Lopez, Joaquin 
dc.contributor.authorAyala, Rosa
dc.date.accessioned2019-05-06T11:35:03Z
dc.date.available2019-05-06T11:35:03Z
dc.date.issued2019-02
dc.identifier.citationHaematologica. 2019 ;104(2):288-296.es_ES
dc.identifier.issn0390-6078es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7540
dc.description.abstractA high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10-4 for single nucleotide variants and 10-5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing-determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P<0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, P=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, P=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.es_ES
dc.description.sponsorshipThis study was supported by the Subdirección General de Investigación Sanitaria (Instituto de Salud Carlos III, Spain) grants PI13/02387 and PI16/01530, and the CRIS against Cancer foundation grant 2014/0120. ML holds a postdoctoral fellowship of the Spanish Ministry of Economy and Competitiveness (FPDI-2013- 16409). PRP holds a postdoctoral fellowship of the Spanish Instituto de Salud Carlos III: Contrato Predoctoral de Formación en Investigación en Salud i-PFIS (IFI 14/00008).es_ES
dc.language.isoenges_ES
dc.publisherFerrata Storti Foundationes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectSTEM-CELL TRANSPLANTATIONes_ES
dc.subjectPROGNOSTIC RELEVANCEes_ES
dc.subjectFLOW-CYTOMETRYes_ES
dc.subjectGENE-MUTATIONSes_ES
dc.subjectDIAGNOSISes_ES
dc.subjectAMLes_ES
dc.subjectRECOMMENDATIONSes_ES
dc.subjectOUTCOMESes_ES
dc.subjectTHERAPYes_ES
dc.titleA novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemiaes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID30093399es_ES
dc.format.volume104es_ES
dc.format.number2es_ES
dc.format.page288-296es_ES
dc.identifier.doi10.3324/haematol.2018.194712es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderCRIS Cancer Foundation (UK)es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1592-8721es_ES
dc.relation.publisherversionhttps://doi.org/10.3324/haematol.2018.194712.es_ES
dc.identifier.journalHaematologicaes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Tumores Hematológicos H12O-CNIOes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/02387es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/01530es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/IFI 14/00008es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional