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CpG IslandMethylator Phenotype Redefines the Prognostic Effect of t(12;21) in Childhood Acute Lymphoblastic Leukemia
Authors: Roman-Gomez, J. (José)
Jimenez-Velasco, A. (A.)
Aguirre, X. (Xavier)
Castillejo, J.A. (J.A.)
Navarro, G. (Germán)
Calasanz-Abinzano, M.J. (Maria Jose)
Garate, L. (Leire)
San-Jose, E. (Edurne)
Cordeu, L. (Lucía)
Prosper, F. (Felipe)
Heiniger, A. (A.)
Torres, A. (Antonio)
Keywords: Materias Investigacion::Ciencias de la Salud::Oncología
Issue Date: 2006
Publisher: American Association for Cancer Research
Publisher version:
ISSN: 1078-0432
Citation: Roman-Gomez, J., Jimenez-Velasco, A., Agirre, X., Castillejo, J. A. et al. CpG IslandMethylator Phenotype Redefines the Prognostic Effect of t(12;21) in Childhood Acute Lymphoblastic Leukemia. Clin Cancer Res 2006; 12; 4845
Purpose: To examine cancer genes undergoing epigenetic inactivation in a set of ETV6/ RUNX1-positive acute lymphoblastic leukemias in order to define the CpG island methylator phenotype (CIMP) in the disease and evaluate its relationship with clinical features and outcome. Experimental Design: Methylation-specific PCRwas used to analyze themethylation status of 38 genes involved in cell immortalization and transformation in 54 ETV6/RUNX1-positive samples in comparison with190 ETV6/RUNX1-negative samples. Results: ETV6/RUNX1-positive samples had at least one gene methylated in 89% of the cases. According to the number of methylated genes observed in each individual sample, 20 patients (37%) were included in the CIMP group (0-2 methylated genes) and 34 (67%) in the CIMP+ group (>2 methylated genes). Remission rate did not differ significantly among either group of patients. Estimated disease-free survival and overall survival at 9 years were 92% and 100% for the CIMP group and 33% and 73% for the CIMP+ group (P =0.002andP = 0.04, respectively). Multivariate analysis showed that methylation profile was an independent prognostic factor in predicting disease-free survival (P = 0.01) and overall survival (P = 0.05). A group of four genes (DKK3, sFRP2, PTEN, andP73) showed specificity for ETV6/RUNX1-positive subset of samples. Conclusion: Our results suggest that methylation profile may be a potential new biomarker of risk prediction in ETV6/RUNX1-positive acute lymphoblastic leukemias.
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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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