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DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia
Authors: Alvarez, S. (Sara)
Suela, J. (Javier)
Valencia, A. (Ana)
Fernandez, A. (Agustín)
Wunderlich, M. (Mark)
Aguirre, X. (Xavier)
Prosper, F. (Felipe)
Martin-Subero, J.I. (Jose Ignacio)
Maiques, A. (Alba)
Acquadro, F. (Francesco)
Rodriguez-Perales, S. (Sandra)
Calasanz-Abinzano, M.J. (Maria Jose)
Roman-Gomez, J. (José)
Siebert, R. (Reiner)
Mulloy, J.C. (James C.)
Cervera, J. (Jose)
Sanz, M.A. (Miguel A.)
Esteller, M. (Manel)
Cigudosa, J.C. (Juan Cruz)
Keywords: Materias Investigacion::Ciencias de la Salud::Oncología
Issue Date: 2010
Publisher: Public Library of Science
Publisher version:
ISSN: 1932-6203
Citation: Alvarez, S., Suela, J., Valencia, A., Fernandez, A. et al. DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia. PLoS ONE 2010; 5 (8): e12197
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
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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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