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Title: DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia
Author: Ferreira, Humberto J.
Heyn, Holger
Vizoso, Miguel
Moutinho, Cátia
Vidal, Enrique
Gomez, A
Martínez Cardús, Anna
Simó-Riudalbas, Laia
Moran, Sebastian
Jost, E
Esteller, Manel
Keywords: Leucèmia mieloide
Myeloid leukemia
Issue Date: 5-Oct-2015
Publisher: Macmillan Publishers
Abstract: Close to half of de novo acute myeloid leukemia (AML) cases do not exhibit any cytogenetic aberrations. In this regard, distortion of the DNA methylation setting and the presence of mutations in epigenetic modifier genes can also be molecular drivers of the disease. In recent years, somatic missense mutations of the DNA methyltransferase 3A (DNMT3A) have been reported in ~20% of AML patients; however, no obvious critical downstream gene has been identified that could explain the role of DNMT3A in the natural history of AML. Herein, using whole-genome bisulfite sequencing and DNA methylation microarrays, we have identified a key gene undergoing promoter hypomethylation-associated transcriptional reactivation in DNMT3 mutant patients, the leukemogenic HOX cofactor MEIS1. Our results indicate that, in the absence of mixed lineage leukemia fusions, an alternative pathway for engaging an oncogenic MEIS1-dependent transcriptional program can be mediated by DNMT3A mutations.
Note: Reproducció del document publicat a:
It is part of: Oncogene, 2016, vol. 35, p. 3079-3082
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ISSN: 0950-9232
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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