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

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.

• Authors: Jing Zhou, Xing Chen, Pan Zhou, Xiaolu Sun, Yangpeng Chen, Mengke Li, Yajing Chu, Jianfeng Zhou, Xuelian Hu, Yi Luo, Weiping Yuan, Gaoxiang Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 600 Pg. 29-34 (04 16 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35182972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Osteopontin

Topics

• Animals
• Apoptosis
• Humans
• Leukemia, Myeloid, Acute (pathology)
• Mice
• Neoplastic Stem Cells (pathology)
• Osteopontin (genetics, metabolism)