1. Osteopontin is required for the maintenance of leukemia stem cells in acute myeloid leukemia.
- Author
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Zhou, Jing, Chen, Xing, Zhou, Pan, Sun, Xiaolu, Chen, Yangpeng, Li, Mengke, Chu, Yajing, Zhou, Jianfeng, Hu, Xuelian, Luo, Yi, Yuan, Weiping, and Wang, Gaoxiang
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ACUTE myeloid leukemia , *STEM cells , *MYELOID cells , *OSTEOPONTIN , *HEMATOLOGIC malignancies - Abstract
Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. The clinical significance of Leukemia stem cells (LSCs) plays an important role in the generation of AML and is the main cause of the recurrence after remission. Osteopontin (OPN), an extracellular matrix protein, has been implicated in hematopoietic malignancies. However, the specific role and the underlying mechanism of AML cell autocrined OPN in leukemia maintenance remain unknown. Here, we showed that knockdown of Opn expression significantly prolonged the survival of mice with MLL-AF9 cell-induced AML and markedly reduced the tumor burden. The LSCs from the Opn-knockdown groups exhibited decreased numbers and impaired function as determined by immunophenotype, colony-forming and limiting dilution assays. Further analysis revealed that Opn prevents LSCs from undergoing apoptosis and cell cycle arrest. Repression of OPN in human AML cell lines in vitro mimics the phenotypes observed in the mouse model. Overall, our data indicated that OPN is a potent therapeutic target for eradicating LSCs in AML. • Inactivation of OPN prolongs survival of MLL-AF9 -induced AML. • OPN maintains LSC mainly by inhibiting apoptosis and accelerating proliferation. • OPN can be a promising therapeutic target for AML. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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