癌症研究
造血
白血病
髓系白血病
骨髓
髓样
基因敲除
细胞生长
生物
下调和上调
干细胞
细胞培养
细胞生物学
免疫学
生物化学
遗传学
基因
作者
Xiaomin He,Yilu Xu,Dan Huang,Yu Zhang,Jing Yu,Li Xie,Ligen Liu,Ye Yu,Chiqi Chen,Jing Wan,Yaping Zhang,Junke Zheng
出处
期刊:Leukemia
[Springer Nature]
日期:2022-11-23
卷期号:37 (2): 265-275
被引量:3
标识
DOI:10.1038/s41375-022-01759-y
摘要
How bone marrow niches regulate leukemogenic activities of leukemia-initiating cells (LICs) is unclear. The present study revealed that the metabolic niche component, ATP, efficiently induced ion influx in LICs through its ligand-gated ion channel, P2X1. P2X1 deletion impaired LIC self-renewal capacities and resulted in an approximately 8-fold decrease in functional LIC numbers in a murine acute myeloid leukemia (AML) model without affecting normal hematopoiesis. P2X1 phosphorylation at specific sites of S387 and T389 was essential for sustaining its promoting effects on leukemia development. ATP-P2X1-mediated signaling upregulated the PBX3 level to transactivate BCAT1 to maintain LIC fates. P2X1 knockdown inhibited the proliferation of both human AML cell lines and primary cells. The P2X1 antagonist sufficiently suppressed AML cell proliferation. These results provided a unique perspective on how metabolic niche factor ATP fine-tunes LIC activities, which may benefit the development of strategies for targeting LICs or other cancer stem cells.
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