A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia

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dc.contributor.author Onecha, Esther
dc.contributor.author Linares, María
dc.contributor.author Rapado, Inmaculada
dc.contributor.author Ruiz-Heredia, Yanira
dc.contributor.author Martínez-Sánchez, Pilar
dc.contributor.author Cedena, Teresa
dc.contributor.author Pratcorona, Marta
dc.contributor.author Pçerez Oteyza, Jaime
dc.contributor.author Herrera, Pilar
dc.contributor.author Barragan, Eva
dc.contributor.author Montesinos, Pau
dc.contributor.author García Vela, José Antonio
dc.contributor.author Magro, Elena
dc.contributor.author Anguita, Eduardo
dc.contributor.author Figuera, Ángela
dc.contributor.author Riaza, Rosalía
dc.contributor.author Martínez-Barranco, Pilar
dc.contributor.author Sánchez-Vega, Beatriz
dc.contributor.author Nomdedeu, Josep
dc.contributor.author Gallardo, Miguel
dc.contributor.author Martínez-López, Joaquín
dc.contributor.author Ayala, Rosa
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.date.accessioned 2019-09-16T11:21:35Z
dc.date.available 2019-09-16T11:21:35Z
dc.date.issued 2019-01-31
dc.identifier.citation Haematologica 104.2 (2019): 288-296 es_ES
dc.identifier.issn 0390-6078 (print) es_ES
dc.identifier.issn 1592-8721 (online) es_ES
dc.identifier.uri http://hdl.handle.net/10486/688590
dc.description.abstract A 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 en_US
dc.description.sponsorship This 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). en_US
dc.format.extent 9 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Ferrata Storti Foundation en_US
dc.relation.ispartof Haematologica es_ES
dc.rights © 2019 Ferrata Storti Foundation en_US
dc.subject.other Myeloid leukemia en_US
dc.subject.other NPM1, IDH1/2 and/or FLT3-single en_US
dc.subject.other Multivariate analysis en_US
dc.subject.other Sequencing en_US
dc.title A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.3324/haematol.2018.194712 es_ES
dc.identifier.doi 10.3324/haematol.2018.194712 es_ES
dc.identifier.publicationfirstpage 288 es_ES
dc.identifier.publicationissue 2 es_ES
dc.identifier.publicationlastpage 296 es_ES
dc.identifier.publicationvolume 104 es_ES
dc.relation.projectID Gobierno de España. PI13/02387 es_ES
dc.relation.projectID Gobierno de España. PI16/01530 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento – NoComercial es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Figuera Álvarez, Ángela (259770)

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