TY  - JOUR
AU  - An, Jungeun
AU  - González-Avalos, Edahí
AU  - Chawla, Ashu
AU  - Jeong, Mira
AU  - López-Moyado, Isaac F
AU  - Li, Wei
AU  - Goodell, Margaret A
AU  - Chavez, Lukas
AU  - Ko, Myunggon
AU  - Rao, Anjana
TI  - Acute loss of TET function results in aggressive myeloid cancer in mice.
JO  - Nature Communications
VL  - 6
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-02160
SP  - 10071 
PY  - 2015
AB  - 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.
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - Histones (NLM Chemicals)
KW  - Proto-Oncogene Proteins (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Tet2 protein, mouse (NLM Chemicals)
KW  - Tet3 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26607761
C2  - pmc:PMC4674670
DO  - DOI:10.1038/ncomms10071
UR  - https://inrepo02.dkfz.de/record/126045
ER  -