期刊
CANCER CELL
卷 16, 期 5, 页码 390-400出版社
CELL PRESS
DOI: 10.1016/j.ccr.2009.09.036
关键词
-
资金
- European Commission
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- Swedish Research Council
- HFSP
- MRC
- Medical Research Council [G0700711B] Funding Source: researchfish
We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBP alpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBP alpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBP alpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据