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

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 disea...

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Autores: Onecha. Esther, Linares Gómez, María, Rapado, Inmaculada, Ruiz-Heredia, Yanira, Martínez Sánchez, María Del Pilar, Cedena Romero, M. Teresa, Pratcorona, Marta, Perez Oteyza, Jaime, Herrera, Pilar, Barragan, Eva, Montesinos, Pau, Garcia Vela, Jose Antonio, Magro, Elena, Anguita Mandly, Eduardo Luis, Figuera, Angela, Riaza, Rosalia, Martínez Barranco, María Pilar, Sanchez-Vega, Beatriz, Nomdedeu, Josep, Gallardo, Miguel, Ayala Díaz, Rosa María, Martínez López, Joaquín
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/93581
Acceso en línea:https://hdl.handle.net/20.500.14352/93581
Access Level:acceso abierto
Palabra clave:616-006.04
Ciencias Biomédicas
24 Ciencias de la Vida
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spelling A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemiaOnecha. EstherLinares Gómez, MaríaRapado, InmaculadaRuiz-Heredia, YaniraMartínez Sánchez, María Del PilarCedena Romero, M. TeresaPratcorona, MartaPerez Oteyza, JaimeHerrera, PilarBarragan, EvaMontesinos, PauGarcia Vela, Jose AntonioMagro, ElenaAnguita Mandly, Eduardo LuisFiguera, AngelaRiaza, RosaliaMartínez Barranco, María PilarSanchez-Vega, BeatrizNomdedeu, JosepGallardo, MiguelAyala Díaz, Rosa MaríaMartínez López, Joaquín616-006.04Ciencias Biomédicas24 Ciencias de la VidaA 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.Ferrata Storti FoundationUniversidad Complutense de Madrid20192019-02-0120192019-02-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/93581reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengPI13 02387 Not availablePI16 01530 Not available2014 0120 Not availableMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 FPDI-2013-16409 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial 4.0 Internationalhttps://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/935812026-06-02T12:44:21Z
dc.title.none.fl_str_mv A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
title A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
spellingShingle A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
Onecha. Esther
616-006.04
Ciencias Biomédicas
24 Ciencias de la Vida
title_short A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
title_full A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
title_fullStr A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
title_full_unstemmed A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
title_sort A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia
dc.creator.none.fl_str_mv Onecha. Esther
Linares Gómez, María
Rapado, Inmaculada
Ruiz-Heredia, Yanira
Martínez Sánchez, María Del Pilar
Cedena Romero, M. Teresa
Pratcorona, Marta
Perez Oteyza, Jaime
Herrera, Pilar
Barragan, Eva
Montesinos, Pau
Garcia Vela, Jose Antonio
Magro, Elena
Anguita Mandly, Eduardo Luis
Figuera, Angela
Riaza, Rosalia
Martínez Barranco, María Pilar
Sanchez-Vega, Beatriz
Nomdedeu, Josep
Gallardo, Miguel
Ayala Díaz, Rosa María
Martínez López, Joaquín
author Onecha. Esther
author_facet Onecha. Esther
Linares Gómez, María
Rapado, Inmaculada
Ruiz-Heredia, Yanira
Martínez Sánchez, María Del Pilar
Cedena Romero, M. Teresa
Pratcorona, Marta
Perez Oteyza, Jaime
Herrera, Pilar
Barragan, Eva
Montesinos, Pau
Garcia Vela, Jose Antonio
Magro, Elena
Anguita Mandly, Eduardo Luis
Figuera, Angela
Riaza, Rosalia
Martínez Barranco, María Pilar
Sanchez-Vega, Beatriz
Nomdedeu, Josep
Gallardo, Miguel
Ayala Díaz, Rosa María
Martínez López, Joaquín
author_role author
author2 Linares Gómez, María
Rapado, Inmaculada
Ruiz-Heredia, Yanira
Martínez Sánchez, María Del Pilar
Cedena Romero, M. Teresa
Pratcorona, Marta
Perez Oteyza, Jaime
Herrera, Pilar
Barragan, Eva
Montesinos, Pau
Garcia Vela, Jose Antonio
Magro, Elena
Anguita Mandly, Eduardo Luis
Figuera, Angela
Riaza, Rosalia
Martínez Barranco, María Pilar
Sanchez-Vega, Beatriz
Nomdedeu, Josep
Gallardo, Miguel
Ayala Díaz, Rosa María
Martínez López, Joaquín
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616-006.04
Ciencias Biomédicas
24 Ciencias de la Vida
topic 616-006.04
Ciencias Biomédicas
24 Ciencias de la Vida
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-02-01
2019
2019-02-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/93581
url https://hdl.handle.net/20.500.14352/93581
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv PI13 02387 Not available
PI16 01530 Not available
2014 0120 Not available
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 FPDI-2013-16409 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 4.0 International
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 4.0 International
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Ferrata Storti Foundation
publisher.none.fl_str_mv Ferrata Storti Foundation
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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