%0 Journal Article
%A An, Jungeun
%A González-Avalos, Edahí
%A Chawla, Ashu
%A Jeong, Mira
%A López-Moyado, Isaac F
%A Li, Wei
%A Goodell, Margaret A
%A Chavez, Lukas
%A Ko, Myunggon
%A Rao, Anjana
%T Acute loss of TET function results in aggressive myeloid cancer in mice.
%J Nature Communications
%V 6
%@ 2041-1723
%C London
%I Nature Publishing Group
%M DKFZ-2017-02160
%P 10071 
%D 2015
%X 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.
%K DNA-Binding Proteins (NLM Chemicals)
%K Histones (NLM Chemicals)
%K Proto-Oncogene Proteins (NLM Chemicals)
%K RNA, Messenger (NLM Chemicals)
%K Tet2 protein, mouse (NLM Chemicals)
%K Tet3 protein, mouse (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26607761
%2 pmc:PMC4674670
%R 10.1038/ncomms10071
%U https://inrepo02.dkfz.de/record/126045