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

To determine the impact of inhibition of KDM1A/LSD1 through genetic manipulation by CRISPR/Cas9 or inducible shRNA or following treatment with irreversible LSD1 inhibitor INCB059872 on global transcriptomic profile in AML and post-MPN sAML cells. To determine the impact of GFI1 knockdown on global transcriptomic profile in AML cells. Overall design: OCI-AML5 cells with or without LSD1 knockout by CRISPR/Cas9, depletion of LSD1 or GFI1 by shRNA, or OCI-AML5 cells that were treated with 1000 nM of irreversible LSD1 inhibitor INCB059872 for 16 hours. Additionally, secondary AML (SET2) and their OTX persister-resistant derivative (SET2 OTX P/R) cells were treated for 16 hours with 250 nM of INCB059872 to determine the effects of LSD1 inhibitor treatment on the global transcriptome profile in parental and BET inhibitor persister-resistant cells. Cells were treated independently and RNA was isolated from biologic replicates and RNA Sequencing was performed.