A critical role of epigenetic inactivation of miR-9 in EVI1high pediatric AML.

Molecular Cancer
Nupur MittalZhijian Qian

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.

References

Oct 24, 2002·Blood·Sahar Barjesteh van Waalwijk van Doorn-KhosrovaniRuud Delwel
Jun 19, 2007·Cancer Research·Vitalyi SenyukGiuseppina Nucifora
Apr 2, 2010·Leukemia·B V BalgobindM M van den Heuvel-Eibrink
Apr 13, 2012·Cancer Science·Keisuke Kataoka, Mineo Kurokawa
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vitalyi SenyukZhijian Qian
Nov 26, 2013·Leukemia·S EmmrichM M van den Heuvel-Eibrink

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Methods Mentioned

BETA
xenograft
flow cytometry

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