HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia

作者:Tian, Chen; Yu, Yong; Jia, Yongsheng; Zhu, Lei; Zhang, Yizhuo*
来源:Annals of Hematology, 2015, 94(9): 1477-1483.
DOI:10.1007/s00277-015-2413-0

摘要

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.