DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia
| Autor: | Javier Suela, Juan C. Cigudosa, Alba Maiques, Agustín F. Fernández, Xabier Agirre, Manel Esteller, Sara Alvarez, Sandra Rodriguez Perales, Mark Wunderlich, Francesco Acquadro, Ana Valencia, José I. Martín-Subero, Felipe Prosper, Miguel A. Sanz, María José Calasanz, José Cervera, Reiner Siebert, Jose Roman-Gomez, James C. Mulloy |
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| Přispěvatelé: | Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Myeloid Oncogene Proteins Fusion lcsh:Medicine Epigenesis Genetic Fusion gene Epigènesi hemic and lymphatic diseases Chromosomes Human lcsh:Science Genetics Multidisciplinary Hematology/Acute Myeloid Leukemia Myeloid leukemia Methylation Middle Aged Prognosis Leukemia Myeloid Acute Leukemia medicine.anatomical_structure DNA methylation Female Karyotypes Metilació Research Article Ciencias de la Salud::Oncología [Materias Investigacion] Adult Leucèmia mieloide Citogenètica Biology Cytogenetics Genetics and Genomics/Epigenetics medicine Humans Epigenetics Genetics and Genomics/Genomics Genetics and Genomics/Cancer Genetics Cariotips Tumor Suppressor Proteins lcsh:R Genetic Variation Adult Acute Myeloid Leukemia DNA Methylation medicine.disease Genetics and Genomics/Disease Models Karyotyping Cancer research lcsh:Q Epigenesis |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona Dadun. Depósito Académico Digital de la Universidad de Navarra PLoS ONE PLoS ONE, Vol 5, Iss 8, p e12197 (2010) |
| Popis: | Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature |
| Databáze: | OpenAIRE |
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