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- Title
A critical role of epigenetic inactivation of miR-9 in EVI1<sup>high</sup> pediatric AML.
- Authors
Mittal, Nupur; Li, Liping; Sheng, Yue; Hu, Chao; Li, Fuxing; Zhu, Tongyu; Qiao, Xiaohong; Qian, Zhijian
- Abstract
Ectopic Viral Integration site 1 (EVI1) upregulation is implicated in 10–25% of pediatric acute myeloid leukemia (AML) and has an inferior outcome with current chemotherapy regimens. Here we report that EVI1 upregulation is associated with methylation of the miR-9 promoter and correlated with downregulation of miR-9 in human AML cell lines and bone marrow (BM) cells from pediatric patients. Reactivation of miR-9 by hypomethylating agents and forced expression of miR-9 in EVI1high leukemia cell lines and primary leukemia cells results in apoptosis and decreased proliferation of EVI1high leukemia cells. Furthermore, re-expression of miR-9 delays disease progression in EVI1high leukemia-xenograft mice. Our results suggest that EVI1-induced hypermethylation and downregulation of the miR-9 plays an important role in leukemogenesis in EVI-1high pediatric AML, indicating that hypomethylating agents may be a potential therapeutic strategy for EVI1high pediatric AML.
- Subjects
ACUTE myeloid leukemia; BONE marrow cells; CELL lines; LEUKEMIA
- Publication
Molecular Cancer, 2019, Vol 18, Issue 1, pN.PAG
- ISSN
1476-4598
- Publication type
Letter
- DOI
10.1186/s12943-019-0952-z