Academic Journal
Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia
| العنوان: | Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia |
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| المؤلفون: | Iria Vázquez, Miren Maicas, José Cervera, Xabier Agirre, Oskar Marin-Béjar, Nerea Marcotegui, Carmen Vicente, Idoya Lahortiga, Maria Gomez-Benito, Claudia Carranza, Ana Valencia, Salut Brunet, Eva Lumbreras, Felipe Prosper, María T. Gómez-Casares, Jesús M. Hernández-Rivas, María J. Calasanz, Miguel A. Sanz, Jorge Sierra, María D. Odero |
| المصدر: | Haematologica, Vol 96, Iss 10 (2011) |
| بيانات النشر: | Ferrata Storti Foundation, 2011. |
| سنة النشر: | 2011 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/6091; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2011.040535 |
| URL الوصول: | https://doaj.org/article/4e460ba7e7eb4f50b9be0966b0a12580 |
| رقم الانضمام: | edsdoj.4e460ba7e7eb4f50b9be0966b0a12580 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2011.040535 |