| First Author | An J | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 10071 | PubMed ID | 26607761 |
| Mgi Jnum | J:228006 | Mgi Id | MGI:5704252 |
| Doi | 10.1038/ncomms10071 | Citation | An J, et al. (2015) Acute loss of TET function results in aggressive myeloid cancer in mice. Nat Commun 6:10071 |
| abstractText | 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. |
