Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia

Promoter hypermethylation plays an important role in the inactivation of cancerrelated genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). To determine the extent of hypermethylation in ALL, we analyzed the meth...

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Detalles Bibliográficos
Autores: Roman-Gomez, J. (José)|||/items/bca25c5c-f92e-4fe2-b9a3-4b722345de85, Jimenez-Velasco, A. (A.)|||/items/c56a1ba7-243e-4226-897d-6d969da1d058, Castillejo, J.A. (J.A.)|||/items/11701cff-259f-4b74-b164-9495896306f7, Aguirre-Ena, X. (Xabier)|||/items/2a000d9c-cb5c-4734-a32c-4fef79998c86, Barrios, M. (M.)|||/items/b136d953-5bc8-42df-a21f-be09564d8fb8, Navarro, G. (Germán)|||/items/b189b5d7-41ed-4f9b-8697-0958ddf51ccb, Molina, F.J. (Francisco J.)|||/items/37b77dfa-464d-4d2a-b2ce-327df1df1458, Calasanz-Abinzano, M.J. (Maria Jose)|||/items/a1f10f5c-06ce-47eb-bfd8-91fb972d8086, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1, Heiniger, A. (A.)|||/items/c1560a2f-8133-4602-856c-ef23edb0a384, Torres, A. (Antonio)|||/items/2ef77e9e-4616-4a3a-b254-b11b17687f35
Tipo de recurso: artículo
Fecha de publicación:2004
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/18564
Acceso en línea:https://hdl.handle.net/10171/18564
Access Level:acceso abierto
Palabra clave:Materias Investigacion::Ciencias de la Salud::Oncología
Área de Terapia Celular
Descripción
Sumario:Promoter hypermethylation plays an important role in the inactivation of cancerrelated genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). To determine the extent of hypermethylation in ALL, we analyzed the methylation status of the CDH1, p73, p16, p15, p57, NES-1, DKK-3, CDH13, p14, TMS-1, APAF-1, DAPK, PARKIN, LATS-1, and PTEN genes in 251 consecutive ALL patients.Atotal of 77.3% of samples had at least 1 gene methylated, whereas 35.9% of cases had 4 or more genes methylated. Clinical features and complete remission rate did not differ among patients without methylated genes, patients with 1 to 3 methylated genes (methylated group A), or patients with more than 3 methylated genes (methylated group B). Estimated disease-free survival (DFS) and overall survival (OS) at 11 years were 75.5% and 66.1%, respectively, for the nonmethylated group; 37.2% and 45.5% for methylated group A; and 9.4% and 7.8% for methylated group B (P < .0001 and P .0004, respectively). Multivariate analysis demonstrated that the methylation profile was an independent prognostic factor in predicting DFS (P < .0001) and OS (P .003). Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in ALL

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