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000126045 1001_ $$aAn, Jungeun$$b0
000126045 245__ $$aAcute loss of TET function results in aggressive myeloid cancer in mice.
000126045 260__ $$aLondon$$bNature Publishing Group$$c2015
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000126045 520__ $$aTET-family dioxygenases oxidize 5-methylcytosine (5mC) in DNA, and exert tumour suppressor activity in many types of cancers. Even in the absence of TET coding region mutations, TET loss-of-function is strongly associated with cancer. Here we show that acute elimination of TET function induces the rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice, pointing to a causative role for TET loss-of-function in this myeloid malignancy. Phenotypic and transcriptional profiling shows aberrant differentiation of haematopoietic stem/progenitor cells, impaired erythroid and lymphoid differentiation and strong skewing to the myeloid lineage, with only a mild relation to changes in DNA modification. We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity.
000126045 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
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000126045 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000126045 650_7 $$2NLM Chemicals$$aHistones
000126045 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins
000126045 650_7 $$2NLM Chemicals$$aRNA, Messenger
000126045 650_7 $$2NLM Chemicals$$aTet2 protein, mouse
000126045 650_7 $$2NLM Chemicals$$aTet3 protein, mouse
000126045 7001_ $$aGonzález-Avalos, Edahí$$b1
000126045 7001_ $$aChawla, Ashu$$b2
000126045 7001_ $$aJeong, Mira$$b3
000126045 7001_ $$aLópez-Moyado, Isaac F$$b4
000126045 7001_ $$aLi, Wei$$b5
000126045 7001_ $$aGoodell, Margaret A$$b6
000126045 7001_ $$0P:(DE-He78)082dd3179733e3e716a58eb90f418a78$$aChavez, Lukas$$b7$$udkfz
000126045 7001_ $$aKo, Myunggon$$b8
000126045 7001_ $$aRao, Anjana$$b9
000126045 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/ncomms10071$$gVol. 6, p. 10071 -$$p10071 $$tNature Communications$$v6$$x2041-1723$$y2015
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