Acute loss of TET function results in aggressive myeloid cancer in mice.
Nat Commun
; 6: 10071, 2015 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-26607761
ABSTRACT
TET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling shows aberrant differentiation of haematopoietic stem/progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Células-Tronco Hematopoéticas
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Leucemia Mieloide
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Proteínas Proto-Oncogênicas
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Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2015
Tipo de documento:
Article