Loss of Asxl2 leads to myeloid malignancies in mice

Jianping Li, Fuhong He, Peng Zhang, Shi Chen, Hui Shi, Yanling Sun, Ying Guo, Hui Yang, Na Man, Sarah Greenblatt, Zhaomin Li, Zhengyu Guo, Yuan Zhou, Lan Wang, Lluis Morey, Sion Williams, Xi Chen, Qun Tian Wang, Stephen D. Nimer, Peng YuQian Fei Wang, Mingjiang Xu, Feng Chun Yang

Producción científica: Articlerevisión exhaustiva

26 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Número de artículo15456
PublicaciónNature communications
Volumen8
DOI
EstadoPublished - jun 8 2017
Publicado de forma externa

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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