2026-05-17T01:15:58Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/261602025-12-18T12:52:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Alvarez, Sara
author
Suela, Javier
author
Valencia, Ana
author
Fernandez, Agustín F
author
Wunderlich, Mark
author
Agirre, Xabier
author
Prósper, Felipe
author
Martín-Subero, José Ignacio
author
Maiques, Alba
author
Acquadro, Francesco
author
Rodriguez Perales, Sandra
author
Calasanz, María José
author
Roman-Gómez, Jose
author
Siebert, Reiner
author
Mulloy, James C
author
Cervera, José
author
Sanz, Miguel Angel
author
Esteller, Manel
author
Cigudosa, Juan C
funder
Instituto de Salud Carlos III
funder
MINISTERIO DE CIENCIA E INNOVACION (ESPAÑA)
funder
KinderKrebsInitiative Buchholz/Holm-Seppensen
funder
Red Tematica de Investigacion sobre Cancer (RETIC)
2025-01-28T09:25:44Z
2025-01-28T09:25:44Z
2010-08-16
PLoS One . 2010 Aug 16;5(8):e12197.
PLos One
20808941
https://hdl.handle.net/20.500.12105/26160
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.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.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.
eng
CPG ISLAND METHYLATION
PREDICTS SURVIVAL
GENE DBCCR1
CELLS
MALIGNANCIES
CANCER
EXPRESSION
DBC1
EPIGENETICS
NEOPLASMS
DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia.
research article
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dnamethylationprofiles-2010.pdf