Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/97043
Title: Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia
Author: Vilas-Zornoza, Amaia
Agirre, Xabier
Martín-Palanco, Vanesa
Martín-Subero, José Ignacio
San José-Eneriz, Edurne
Garate, Leire
Álvarez, Sara
Miranda, Estíbaliz
Rodríguez-Otero, Paula
Rifón, José
Torres, Antonio
Calasanz, María José
Cigudosa, Juan Cruz
Román-Gómez, José
Prósper, Felipe
Keywords: Apoptosi
ADN
Apoptosis
DNA
Issue Date: 28-Feb-2011
Publisher: Public Library of Science (PLoS)
Abstract: Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL). Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-2'-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p<0.001) rate being an independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0017012
It is part of: PLoS One, 2011, vol. 6, num. 2, p. e17012
Related resource: http://dx.doi.org/10.1371/journal.pone.0017012
URI: http://hdl.handle.net/2445/97043
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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