PERK/NRF2 and autophagy form a resistance mechanism against G9a inhibition in leukemia stem cells.

ABSTRACT:

Background

The histone methyltransferase G9a has recently been identified as a potential target for epigenetic therapy of acute myeloid leukemia (AML). However, the effect of G9a inhibition on leukemia stem cells (LSCs), which are responsible for AML drug resistance and recurrence, is unclear. In this study, we investigated the underlying mechanisms of the LSC resistance to G9a inhibition.

Methods

We evaluated the effects of G9a inhibition on the unfolded protein response and autophagy in AML and LSC-like cell lines and in primary CD34⁺CD38^- leukemic blasts from patients with AML and investigated the underlying mechanisms. The effects of treatment on cells were evaluated by flow cytometry, western blotting, confocal microscopy, reactive oxygen species (

SUBMITTER: Jang JE 

PROVIDER: S-EPMC7158163 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature