DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are re...

Descripción completa

Detalles Bibliográficos
Autores: Alvarez, Sara, Suela, Javier, Valencia, Ana, Fernández, Agustín F., Wunderlich, Mark, Agirre, Xabier, Prosper, Felipe, Martín-Subero, José Ignacio, Maiques, Alba, Acquadro, Francesco, Rodriguez Perales, Sandra, Calasanz, María José, Román-Gómez, José, Siebert, Reiner, Mulloy, James C., Cervera, José, Sanz, Miguel Angel, Esteller, Manel, 1968-, Cruz Cigudosa, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/69603
Acceso en línea:https://hdl.handle.net/2445/69603
Access Level:acceso abierto
Palabra clave:Metilació
Cariotips
Leucèmia mieloide
Epigènesi
Citogenètica
Methylation
Karyotypes
Myeloid leukemia
Epigenesis
Cytogenetics
id ES_d75eb7abe51da179770ecb2bc7ab7fe5
oai_identifier_str oai:diposit.ub.edu:2445/69603
network_acronym_str ES
network_name_str España
repository_id_str
spelling DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemiaAlvarez, SaraSuela, JavierValencia, AnaFernández, Agustín F.Wunderlich, MarkAgirre, XabierProsper, FelipeMartín-Subero, José IgnacioMaiques, AlbaAcquadro, FrancescoRodriguez Perales, SandraCalasanz, María JoséRomán-Gómez, JoséSiebert, ReinerMulloy, James C.Cervera, JoséSanz, Miguel AngelEsteller, Manel, 1968-Cruz Cigudosa, JuanMetilacióCariotipsLeucèmia mieloideEpigènesiCitogenèticaMethylationKaryotypesMyeloid leukemiaEpigenesisCytogeneticsBackground: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature.Public Library of Science (PLoS)2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/69603Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0012197PLoS One, 2010, vol. 5, num. 8, p. e12197http://dx.doi.org/10.1371/journal.pone.0012197cc-by (c) Álvarez, Sara et al., 2010http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/696032026-05-27T06:46:51Z
dc.title.none.fl_str_mv DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
title DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
spellingShingle DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
Alvarez, Sara
Metilació
Cariotips
Leucèmia mieloide
Epigènesi
Citogenètica
Methylation
Karyotypes
Myeloid leukemia
Epigenesis
Cytogenetics
title_short DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
title_full DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
title_fullStr DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
title_full_unstemmed DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
title_sort DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
dc.creator.none.fl_str_mv Alvarez, Sara
Suela, Javier
Valencia, Ana
Fernández, Agustín F.
Wunderlich, Mark
Agirre, Xabier
Prosper, Felipe
Martín-Subero, José Ignacio
Maiques, Alba
Acquadro, Francesco
Rodriguez Perales, Sandra
Calasanz, María José
Román-Gómez, José
Siebert, Reiner
Mulloy, James C.
Cervera, José
Sanz, Miguel Angel
Esteller, Manel, 1968-
Cruz Cigudosa, Juan
author Alvarez, Sara
author_facet Alvarez, Sara
Suela, Javier
Valencia, Ana
Fernández, Agustín F.
Wunderlich, Mark
Agirre, Xabier
Prosper, Felipe
Martín-Subero, José Ignacio
Maiques, Alba
Acquadro, Francesco
Rodriguez Perales, Sandra
Calasanz, María José
Román-Gómez, José
Siebert, Reiner
Mulloy, James C.
Cervera, José
Sanz, Miguel Angel
Esteller, Manel, 1968-
Cruz Cigudosa, Juan
author_role author
author2 Suela, Javier
Valencia, Ana
Fernández, Agustín F.
Wunderlich, Mark
Agirre, Xabier
Prosper, Felipe
Martín-Subero, José Ignacio
Maiques, Alba
Acquadro, Francesco
Rodriguez Perales, Sandra
Calasanz, María José
Román-Gómez, José
Siebert, Reiner
Mulloy, James C.
Cervera, José
Sanz, Miguel Angel
Esteller, Manel, 1968-
Cruz Cigudosa, Juan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Metilació
Cariotips
Leucèmia mieloide
Epigènesi
Citogenètica
Methylation
Karyotypes
Myeloid leukemia
Epigenesis
Cytogenetics
topic Metilació
Cariotips
Leucèmia mieloide
Epigènesi
Citogenètica
Methylation
Karyotypes
Myeloid leukemia
Epigenesis
Cytogenetics
description Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature.
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/69603
url https://hdl.handle.net/2445/69603
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0012197
PLoS One, 2010, vol. 5, num. 8, p. e12197
http://dx.doi.org/10.1371/journal.pone.0012197
dc.rights.none.fl_str_mv cc-by (c) Álvarez, Sara et al., 2010
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Álvarez, Sara et al., 2010
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420996633559040
score 15,300724

Similares en LA Referencia