beta-Arrestin1 promotes the self-renewal of the leukemia-initiating cell-enriched subpopulation in B-lineage acute lymphoblastic leukemia related to DNMT1 activity
beta-Arrestin1 promotes the self-renewal of the leukemia-initiating cell-enriched subpopulation in B-lineage acute lymphoblastic leukemia related to DNMT1 activity
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beta-Arrestin1 促进与 DNMT1 活性相关的 B 系急性淋巴细胞白血病中白血病起始细胞富集亚群的自我更新
DOI：
10.1016/j.canlet.2014.11.025
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发表时间：
2015
期刊：
影响因子：
9.7
通讯作者：
Zou Lin
中科院分区：
文献类型：
--
作者：
Shu Yi;Zhou Xiaoyan;Qi Xinkun;Liu Shan;Li Kang;Tan Junjie;Liu Zhidai;Yu Jie;Zhang Penghui;Zou Lin
The self-renewal ability of the leukemia initiating cell-enriched subpopulation is critical for leukemia initiation and maintenance. However, the regulation of leukemia initiating cells for the leukemia progression is poorly understood. In this study, we observed that β-Arrestin1, a multiple-function protein, is elevated in leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients. The loss ofβ-Arrestin1in leukemia initiating cells-enriched fraction attenuates its self-renewal capacity bothin vitroandin vivo. Further experiments showed that the mRNA expression level ofβ-Arrestin1is negatively correlated with that ofPTENin leukemia initiating cells-enriched fraction. Moreover, DNA methylation of thePTENpromoter region, the activity and expression of DNMTs were enhanced in the leukemia initiating cells-enriched fraction. The inhibition of DNMT1 activity impaired the self-renewal and increased expression ofPTENof leukemia initiating cells-enriched fraction. In addition, depletion ofβ-Arrestin1significantly decreased DNMT1 activity andPTENmethylation, and consistently increased PTEN expression in leukemia initiating cells-enriched fraction. Our study reveals a novel function of β-Arrestin1 in the regulation of the self-renewal of leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients related to DNMT1 activity, indicating that β-Arrestin1 is a potential therapeutic target in B-lineage acute lymphoblastic leukemia.
