Abstract
Background
Stem cell marker CD82 plays a vital role in the oncogenesis and progression of acute myelogenous leukemia (AML), especially in sharing properties of leukemia stem cells (LSCs). The Wnt/β-catenin pathway is required for the development of LSCs in AML. The present study aimed to validate whether CD82 supports the survival of LSCs in pediatric AML via activation of Wnt/β-catenin signaling pathway.
Methods
CD82 expression and its correlation with molecules downstream of Wnt/β-catenin pathway in samples from pediatric AML patients were analyzed. Forced or downregulated expression of CD82 in AML cells was evaluated for the effects of CD82 on cell proliferation, cycle regulation, apoptosis, and adriamycin chemoresistance and to validate the underlying mechanism.
Result
Aberrant expression of CD82 in pediatric AML patients was found. CD82 messenger RNA expression correlated positively with downstream molecules of Wnt/β-catenin pathway in AML children. Knockdown of CD82 induced apoptosis, suppressed growth, and decreased adriamycin chemoresistance in AML cells. CD82 accelerated β-catenin nuclear location and then stimulated the expression of downstream molecules of Wnt/β-catenin pathway.
Conclusion
CD82 regulates the proliferation and chemotherapy resistance of AML cells via activation of the Wnt/β-catenin pathway, which suggest that the CD82 may be a potential therapeutic target in AML children.
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Acknowledgements
This research was funded by Shandong provincial Government Science Foundation, grant number 2016GSF201189.
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Contributions to conception and design, P.Z. and H.J. Acquisition and analysis of data: H.J., L.C., and Y.X. Drafting and revising the article, H.J., S.L., and J.D. Final approval of the version to be published, P.Z. and Y.W.
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Ji, H., Chen, L., Xing, Y. et al. CD82 supports survival of childhood acute myeloid leukemia cells via activation of Wnt/β-catenin signaling pathway. Pediatr Res 85, 1024–1031 (2019). https://doi.org/10.1038/s41390-019-0370-3
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DOI: https://doi.org/10.1038/s41390-019-0370-3
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