Targeted inhibition of GFI1/KDM1A combined with BET inhibitor augments lethal activity against AML including post-MPN sAML cells [ATAC-seq]

To determine the impact of inhibition of KDM1A/LSD1 through genetic manipulation or with irreversible LSD1 inhibitors on global chromatin accessibility and occupancy of H3K27Ac and BRD4 in AML and post-MPN sAML cells. Examination of Acetylated K27 histone H3 modification and BRD4 occupancy by ChIP-Seq analysis and chromatin accessibility by ATAC-Seq analysis in AML OCI-AML5 cells with CRISPR/Cas9 mediated knockout of KDM1A or following treatment with an irreversible inhibitor of LSD1 (INCB059872). Examination of BRD4 occupancy in untreated and OTX015-treated cells. Examination of chromatin accessibility in secondary AML SET2 and its OTX persister resistant derivative (SET-2-OTX P/R) following treatment with INCB059872.