Abstract
Although aberrant Notch activation contributes to leukemogenesis in T cells, the role of Notch pathway in acute myeloid leukemia (AML) remains controversial. To address this issue, we compared the expression levels of its downstream effector HES1 and p21 in bone marrow mononuclear cells (BMNCs) from 30 newly diagnosed AML patients and three AML cell lines to normal BMNCs. The results showed that both of them were downregulated in AML cells. In vitro, induced activation of HES1 by retrovirus in AML cell lines consistently led to AML cell growth arrest and apoptosis induction, which was associated with enhanced p21 expression. Furthermore, overexpression of HES1 in primary AML cells inhibited growth of AML in a xenograft mice model. In conclusion, we demonstrated the tumor suppressor role of HES1 in AML.
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (31301161, 81270603) and Tianjin Natural Science Foundation of China (13JCYBJC22800).
Authors’ contribution
Chen Tian did all the experiments and wrote the paper; Lei Zhu, Yongsheng Jia, and Yong Yu provided clinical samples and information; Yizhuo Zhang designed the experiments, interpreted the data, and wrote the manuscript.
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The authors declare that they have no conflict of interest.
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Tian, C., Yu, Y., Jia, Y. et al. HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia. Ann Hematol 94, 1477–1483 (2015). https://doi.org/10.1007/s00277-015-2413-0
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DOI: https://doi.org/10.1007/s00277-015-2413-0