Web of Science: 34 citations, Scopus: 37 citations, Google Scholar: citations
Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia
Vázquez, Iria (Universidad de Navarra. CIMA)
Maicas, Miren (Universidad de Navarra. Departamento de Genética)
Cervera, José (Hospital Universitario La Fe)
Agirre, Xabier (Universidad de Navarra. CIMA)
Marin-Béjar, Oskar (Universidad de Navarra. CIMA)
Marcotegui, Nerea (Universidad de Navarra. CIMA)
Vicente, Carmen (Universidad de Navarra. CIMA)
Lahortiga, Idoya (Human Genome Laboratory. Department of Molecular and Developmental Genetics. VIB)
Gomez-Benito, Maria (Universidad de Navarra. CIMA)
Carranza, Claudia (Instituto de Investigación Genética (Milpas Altas, Guatemala))
Valencia, Ana (Hospital Universitario La Fe)
Brunet, Salut (Institut d'Investigació Biomèdica Sant Pau)
Lumbreras, Eva (Universidad de Salamanca. Hospital Universitario de Salamanca y CSIC)
Prosper, Felipe (Universidad de Navarra. CIMA)
Gómez-Casares, Maria Teresa (Hospital Dr. Negrin (Las Palmas de Gran Canaria))
Hernández-Rivas, Jesús M. (Universidad de Salamanca. Hospital Universitario de Salamanca y CSIC)
Calasanz, María J. (Universidad de Navarra. Departamento de Genética)
Sanz, Miguel A. (Hospital Universitario La Fe)
Sierra Gil, Jorge (Institut d'Investigació Biomèdica Sant Pau)
Odero, María D. (Universidad de Navarra. Departamento de Genética)

Date: 2011
Abstract: Background: 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.
Note: Altres ajuts: Asociación Española Contra el Cáncer, Departamento Salud del Gobierno de Navarra(14/2008), Fundación Cellex, SACYL(355/4/09), Fundación para la Investigación Médica Aplicada y UTE
Note: Número d'acord de subvenció MICINN/SAF2005/06425
Note: Número d'acord de subvenció MICINN/PI081687
Note: Número d'acord de subvenció AGAUR/2009-SGR-1246
Note: Número d'acord de subvenció ISCIII/RTICC/RD06/0020/0078
Note: Número d'acord de subvenció ISCIII/RTICC/RD06/0020/0101
Note: Número d'acord de subvenció ISCIII/RTICC/RD06/0020/0006
Note: Número d'acord de subvenció ISCIII/RTICC/RD06/0020/0031
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: AML ; EVI1 ; Overexpression ; 3q ; Epigenetics
Published in: Haematologica, Vol. 96, Núm. 10 (october 2011) , p. 1448-1456, ISSN 1592-8721

DOI: 10.3324/haematol.2011.040535
PMID: 21750091


9 p, 765.5 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2019-05-20, last modified 2019-12-23



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