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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Terapia celular > DA - CIMA - Oncología - Terapia celular - Artículos de Revista >

Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia
Authors: Roman-Gomez, J. (José)
Cordeu, L. (Lucía)
Aguirre, X. (Xavier)
Jimenez-Velasco, A. (A.)
San-Jose, E. (Edurne)
Garate, L. (Leire)
Calasanz, M.J. (María José)
Heiniger, A. (A.)
Torres, A. (Antonio)
Prosper, F. (Felipe)
Keywords: Materias Investigacion::Ciencias de la Salud::Oncología
Issue Date: 2007
Publisher: American Society of Hematology
Publisher version: http://bloodjournal.hematologylibrary.org/
ISSN: 0006-4971
Citation: Román-Gómez, J., Cordeu, L., Agirre, X., Jiménez-Velasco, A. et al. Blood. 2007;109: 3462-3469
Abstract
Activation of the Wnt/ -catenin signaling pathway is a hallmark of a number of solid tumors. We analyzed the regulation of the Wnt/ -catenin pathway in acute lymphoblastic leukemia (ALL) and its role in the pathogenesis of the disease. We found that expression of the Wnt inhibitors sFRP1, sFRP2, sFRP4, sFRP5, WIF1, Dkk3, and Hdpr1 was down-regulated due to abnormal promoter methylation in ALL cell lines and samples from patients with ALL. Methylation of Wnt inhibitors was associated with activation of the Wntsignaling pathway as demonstrated by the up-regulation of the Wnt target genes WNT16, FZ3, TCF1, LEF1, and cyclin D1 in cell lines and samples and the nuclear localization of -catenin in cell lines. Treatment of ALL cells with the Wnt inhibitor quercetin or with the demethylating agent 5-aza-2 -deoxycytidine induced an inactivation of the Wnt pathway and induced apoptosis of ALL cells. Finally, in a group of 261 patients with newly diagnosed ALL, abnormal methylation of Wnt inhibitors was associated with decreased 10- year disease-free survival (25% versus 66% respectively, P < .001) and overall survival (28% versus 61% respectively, P .001). Our results indicate a role of abnormal Wnt signaling in ALL and establish a group of patients with a significantly worse prognosis (methylated group).
Permanent link: http://hdl.handle.net/10171/17735
Appears in Collections:DA - CIMA - Oncología - Síndromes mieloproliferativos - Artículos de Revista
DA - CIMA - Oncología - Terapia celular - Artículos de Revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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