Osteopontin is required for the maintenance of leukemia stem cells in acute myeloid leukemia.

Feb 21, 2022

Contributor: Jing Zhou,Xing Chen,Pan Zhou,Xiaolu Sun,Yangpeng Chen,Mengke Li,Yajing Chu,Jianfeng Zhou,Xuelian Hu,Yi Luo,Weiping Yuan,Gaoxiang Wang

Osteopontin is required for the maintenance of leukemia stem cells in acute myeloid leukemia.

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.
Copyright © 2022 Elsevier Inc. All rights reserved.

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About The Expert

Jing Zhou

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Xing Chen

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Pan Zhou

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Xiaolu Sun

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Yangpeng Chen

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Mengke Li

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Yajing Chu

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.

Jianfeng Zhou

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Xuelian Hu

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Yi Luo

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Weiping Yuan

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. Electronic address: wpyuan@ihcams.ac.cn.

Gaoxiang Wang

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address: gxwtjxy@126.com.

References

PubMed