ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway

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作者
Wen Liu
Xiaoying Zhu
Ling Tang
Na Shen
Fanjun Cheng
Ping Zou
Yong You
Guolin Yuan
Qing Li
Xiaojian Zhu
机构
[1] Huazhong University of Science and Technology,Institute of Hematology, Union Hospital, Tongji Medical College
[2] The First Affiliated Hospital of Zhengzhou University,Department of Hematology
[3] Affiliated Hospital of Hubei University of Arts and Science,Department of Hematology
[4] Wuhan No. 1 Hospital,Department of Hematology
[5] Huazhong University of Science and Technology,Department of Hematology, Tongji Hospital, Tongji Medical College
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Although tyrosine kinase inhibitors (TKIs) improve the prognosis of chronic myeloid leukemia (CML) patients, resistance to TKIs and residual leukemia stem cells (LSCs) inevitably become the bottleneck of cure. Therefore, we need to explore novel treatment strategies based on conventional treatment strategies. Our previous study found that CML cell senescence may be one of the main factors to achieve clinical cure of CML. Studies have shown that lipid metabolism plays a key role in cellular senescence. Here, we found that long-chain acyl-CoA synthetase 1 (ACSL1) was significantly up-regulated in senescent CML cells. Furthermore, we demonstrated that overexpression of ACSL1 induces senescence and inhibits cell growth in K562 cells by altering cell cycle progression, and enhances the proliferation-inhibiting effect of imatinib. Overexpression of ACSL1 enhances imatinib-induced tumorigenic decline in K562 cells in vivo. Knockdown of ACSL1 reverses imatinib-induced senescence in K562 cells. Mechanistically, overexpression of ACSL1 induced senescence in K562 cells via the SIRT1/p53/p21 axis. Collectively, our study showed that ACSL1 promotes imatinib-induced K562 cells senescence and tumor growth by regulating SIRT1/p53/p21 pathway. The ACSL1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CML and a new potential target for eradication of CML LSCs.
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