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.
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 leukemiapatients 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 H3lysine 4. Conversely, cell lines with no expression of EVI1 have DNA hypermethylation and are marked by repressive trimethylation of histone H3lysine 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 leukemiapatients 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 H3lysine 4 and histone H3lysine 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.
Authors: M L Mucenski; B A Taylor; J N Ihle; J W Hartley; H C Morse; N A Jenkins; N G Copeland Journal: Mol Cell Biol Date: 1988-01 Impact factor: 4.272
Authors: R Wieser; A Volz; S Schnittger; U Jäger; H Grüner; J G Meran; K Wimmer; A Ziegler; C Fonatsch Journal: Br J Haematol Date: 2000-08 Impact factor: 6.998
Authors: M Nakao; S Yokota; T Iwai; H Kaneko; S Horiike; K Kashima; Y Sonoda; T Fujimoto; S Misawa Journal: Leukemia Date: 1996-12 Impact factor: 11.528
Authors: Lilia Suárez; María Belén Vidriales; María-José Moreno; Antonio López; José García-Laraña; Cristina Pérez-López; Mar Tormo; Esperanza Lavilla; María Consuelo López-Berges; María de Santiago; Jesús F San Miguel; Alberto Orfao Journal: Haematologica Date: 2005-01 Impact factor: 9.941
Authors: Peter J M Valk; Roel G W Verhaak; M Antoinette Beijen; Claudia A J Erpelinck; Sahar Barjesteh van Waalwijk van Doorn-Khosrovani; Judith M Boer; H Berna Beverloo; Michael J Moorhouse; Peter J van der Spek; Bob Löwenberg; Ruud Delwel Journal: N Engl J Med Date: 2004-04-15 Impact factor: 91.245
Authors: Idoya Lahortiga; Iria Vázquez; Xabier Agirre; María J Larrayoz; José L Vizmanos; Alessandro Gozzetti; María J Calasanz; María D Odero Journal: Genes Chromosomes Cancer Date: 2004-07 Impact factor: 5.006
Authors: Sahar Barjesteh van Waalwijk van Doorn-Khosrovani; Claudia Erpelinck; Wim L J van Putten; Peter J M Valk; Sonja van der Poel-van de Luytgaarde; Ronald Hack; Rosalyn Slater; Elisabeth M E Smit; H Berna Beverloo; Gregor Verhoef; Leo F Verdonck; Gert J Ossenkoppele; Pieter Sonneveld; Georgine E de Greef; Bob Löwenberg; Ruud Delwel Journal: Blood Date: 2002-10-03 Impact factor: 22.113
Authors: John Timothy Caldwell; Holly Edwards; Alan A Dombkowski; Steven A Buck; Larry H Matherly; Yubin Ge; Jeffrey W Taub Journal: PLoS One Date: 2013-07-10 Impact factor: 3.240