Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia

The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 p...

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Detalles Bibliográficos
Autores: Martin, V. (Vanesa)|||/items/eaaaf671-912b-4185-95e4-8ff8a3da3b9b, Aguirre-Ena, X. (Xabier)|||/items/2a000d9c-cb5c-4734-a32c-4fef79998c86, Jimenez-Velasco, A. (A.)|||/items/c56a1ba7-243e-4226-897d-6d969da1d058, San-José-Enériz, E. (Edurne)|||/items/1c6714b1-f536-4b57-a755-83eca42e9964, Cordeu, L. (Lucía)|||/items/9360af5e-bc98-4917-b059-eb7e42e4bd2d, Garate-Iturriagagoitia, L. (Leire)|||/items/8cb76f28-d2ce-4a71-a8b9-3e3e37a120a3, Vilas, A. (Amaia)|||/items/cebdc859-3ba2-4e25-b0e4-6a230b97a14f, Castillejo, J.A. (J.A.)|||/items/11701cff-259f-4b74-b164-9495896306f7, Heiniger, A. (A.)|||/items/c1560a2f-8133-4602-856c-ef23edb0a384, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1, Torres, A. (Antonio)|||/items/2ef77e9e-4616-4a3a-b254-b11b17687f35, Roman-Gomez, J. (José)|||/items/bca25c5c-f92e-4fe2-b9a3-4b722345de85
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/18357
Acceso en línea:https://hdl.handle.net/10171/18357
Access Level:acceso abierto
Palabra clave:Materias Investigacion::Ciencias de la Salud::Oncología
Área de Terapia Celular
Descripción
Sumario:The clinical significance of aberrant promoter methylation of the canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor gene Wnt5a, belonging to the non-canonical Wnt signaling pathway, was investigated in a large series of 75 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by methylationspecific polymerase chain reaction. At least one methylated gene was observed in cells from 66% (49/75) of patients (methylated group). Disease-free survival and overall survival at 9 years were 51 and 40%, respectively, for the unmethylated group and 3 and 2%, respectively, for the methylated group (both P < 0.0001). Multivariate analysis demonstrated that the Wnt methylation profile was an independent prognostic factor predicting disease-free survival (P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation of promoter-associated CpG islands in the Wnt signaling pathway is very common in Philadelphia chromosome-positive acute lymphoblastic leukemia and potentially defines subgroups with distinct clinical characteristics.

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