期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15456
关键词
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资金
- National Institutes of Health [CA172408, CA185751, HL112294]
- National Key Basic Research Program of China [2014CB542001]
- External Cooperation Program of BIC
- Chinese Academy of Sciences [153F11KYSB20150013]
- National Natural Science Foundation of China [81470340]
- Youth Innovation Promotion Association of Chinese Academy of Sciences
ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8; 21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2(-/-) mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2(-/-) and Asxl2(+/-) BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia. Paired daughter cell assays demonstrate that Asxl2 loss enhances the self-renewal of HSCs. Deletion of Asxl2 alters the expression of genes critical for HSC self-renewal, differentiation and apoptosis in Lin(-) cKit(+) cells. The altered gene expression is associated with dysregulated H3K27ac and H3K4me1/2. Our study demonstrates that ASXL2 functions as a tumour suppressor to maintain normal HSC function.
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