Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia

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dc.contributor.authorVázquez Urio, Iria
dc.contributor.authorMaicas, Miren
dc.contributor.authorCervera, José
dc.contributor.authorAgirre, Xabier
dc.contributor.authorMarin-Béjar, Oskar
dc.contributor.authorMarcotegui, Nerea
dc.contributor.authorVicente, Carmen
dc.contributor.authorLahortiga, Idoya
dc.contributor.authorGómez-Benito, María
dc.contributor.authorCarranza, Claudia
dc.contributor.authorValencia, Ana
dc.contributor.authorBrunet, Salut
dc.contributor.authorLumbreras, Eva
dc.contributor.authorPrósper, Felipe
dc.contributor.authorGómez-Casares, Teresa
dc.contributor.authorHernández-Rivas, Jesús M.
dc.contributor.authorCalasanz, María José
dc.contributor.authorSanz, Miguel A.
dc.contributor.authorSierra, Jorge
dc.contributor.authorOdero, María D.
dc.contributor.departmentCienciases_ES
dc.contributor.departmentZientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernua
dc.date.accessioned2025-01-14T10:31:55Z
dc.date.available2025-01-14T10:31:55Z
dc.date.issued2012-10-18
dc.date.updated2025-01-14T10:18:35Z
dc.description.abstractBackground The EVI1 gene (3q26) codes for a zinc finger transcription factor with important roles in both mammalian development and leukemogenesis. Over-expression of EVI1 through either 3q26 rearrangements, MLL fusions, or other unknown mechanisms confers a poor prognosis in acute myeloid leukemia. Design and Methods We analyzed the prevalence and prognostic impact of EVI1 over-expression in a series of 476 patients with acute myeloid leukemia, and investigated the epigenetic modifications of the EVI1 locus which could be involved in the transcriptional regulation of this gene. Results Our data provide further evidence that EVI1 over-expression is a poor prognostic marker in acute myeloid leukemia patients less than 65 years old. Moreover, we found that patients with no basal expression of EVI1 had a better prognosis than patients with expression/over-expression (P=0.036). We also showed that cell lines with over-expression of EVI1 had no DNA methylation in the promoter region of the EVI1 locus, and had marks of active histone modifications: H3 and H4 acetylation, and trimethylation of histone H3 lysine 4. Conversely, cell lines with no expression of EVI1 have DNA hypermethylation and are marked by repressive trimethylation of histone H3 lysine 27 at the EVI1 promoter. Conclusions Our results identify EVI1 over-expression as a poor prognostic marker in a large, independent cohort of acute myeloid leukemia patients less than 65 years old, and show that the total absence of EVI1 expression has a prognostic impact on the outcome of such patients. Furthermore, we demonstrated for the first time that an aberrant epigenetic pattern involving DNA methylation, H3 and H4 acetylation, and trimethylation of histone H3 lysine 4 and histone H3 lysine 27 might play a role in the transcriptional regulation of EVI1 in acute myeloid leukemia. This study opens new avenues for a better understanding of the regulation of EVI1 expression at a transcriptional level.en
dc.description.sponsorshipThis work was supported by grants from the Ministerio Educación y Ciencia (SAF2005/06425), Ministerio Ciencia e Innovación (PI081687), AECC, Departamento Salud del Gobierno de Navarra (14/2008), Generalitat de Catalunya (2009-SGR-1246), Fundación Cellex, SACYL (355/4/09), ISCIII-RTICC (RD06/0020/0078, RD06/0020/0101, RD06/0020/0006, RD06/0020/0031), and Fundación para la Investigación Médica Aplicada y UTE (Spain).
dc.format.mimetypeapplication/pdfen
dc.identifier.citationVázquez, I., Maicas, M., Cervera, J., Agirre, X., Marin-Béjar, O., Marcotegui, N., Vicente, C., Lahortiga, I., Gomez-Benito, M., Carranza, C., Valencia, A., Brunet, S., Lumbreras, E., Prosper, F., Gómez-Casares, M. T., Hernández-Rivas, J. M., Calasanz, M. J., Sanz, M. A., Sierra, J., Odero, M. D. (2011). Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia. Haematologica, 96(10), 1448-1456. https://doi.org/10.3324/haematol.2011.040535.
dc.identifier.doi10.3324/haematol.2011.040535
dc.identifier.issn1592-8721
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/52913
dc.language.isoeng
dc.publisherFerrata Storti Foundation
dc.relation.ispartofHaematologica (2011), vol. 96, núm. 10
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN//PI081687/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//14%2F2008/
dc.relation.publisherversionhttps://doi.org/10.3324/haematol.2011.040535
dc.rights©2011 Ferrata Storti Foundation. This is an open-access paper
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject3qen
dc.subjectAMLen
dc.subjectEpigeneticsen
dc.subjectEVI1en
dc.subjectOverexpressionen
dc.titleDown-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemiaen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication3762d67a-d18f-4f29-8eee-8b4c20793cd8
relation.isAuthorOfPublication.latestForDiscovery3762d67a-d18f-4f29-8eee-8b4c20793cd8

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