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| Pàgina inicial > Articles > Articles publicats > Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia |
(Universidad de Navarra. Departamento de Bioquímica y Genética) (Hospital Universitari i Politècnic La Fe (València)) (Clínica Universidad de Navarra. Centro de Investigación Médica Aplicada) (Clínica Universidad de Navarra. Centro de Investigación Médica Aplicada) (Institut d'Investigació Biomèdica Sant Pau) (Clínica Universidad de Navarra. Centro de Investigación Médica Aplicada) (Hospital Universitario de Gran Canaria Dr. Negrín) (Hospital Universitario de Salamanca) (Universidad de Navarra. Departamento de Bioquímica y Genética) (Hospital Universitari i Politècnic La Fe (València))| Data: | 2011 |
| Resum: | 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. |
| Ajuts: | Ministerio de Ciencia e Innovación SAF2005/06425 Ministerio de Ciencia e Innovación PI081687 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-1246 Instituto de Salud Carlos III RTICC/RD06/0020/0078 Instituto de Salud Carlos III RTICC/RD06/0020/0101 Instituto de Salud Carlos III RTICC/RD06/0020/0006 Instituto de Salud Carlos III RTICC/RD06/0020/0031 |
| Nota: | 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 |
| Drets: | 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | AML ; EVI1 ; Overexpression ; 3q ; Epigenetics |
| Publicat a: | Haematologica, Vol. 96, Núm. 10 (october 2011) , p. 1448-1456, ISSN 1592-8721 |
