Scientific publications

Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia

Román-Gómez J, Cordeu L, Agirre X, Jiménez-Velasco A, San José-Eneriz E, Garate L, Calasanz MJ, Heiniger A, Torres A, Prosper F.
Department of Hematology, Hospital Reina Sofia, Cordoba, Spain.

Magazine: Blood

Date: Apr 15, 2007

Cell Therapy Area [SP]

Activation of the Wnt/beta-catenin signaling pathway is a hallmark of a number of solid tumors. We analyzed the regulation of the Wnt/beta-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 Wnt-signaling 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 beta-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).

CITATION  Blood. 2007 Apr 15;109(8):3462-9



The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra


The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra


Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra