Global gene expression alterations caused by depletion of RUNX1 in AML cells are opposite to the expression signature induced by correction of RUNX1 mutation in induced pluripotent stem cells (IPSCs) from a patient with FPD/AML. (A) RNA-Seq analysis of OCI-AML5 cells transduced with sh NT or RUNX1 shRNA for 72 hours. The heat map shows the number of upregulated and downregulated genes with a fold change ≥1.5 and a P value < .05. (B) Log2 fold-change of selected mRNA expression alterations resulting from knockdown of RUNX1 in OCI-AML5 cells. (C) Comparison of the gene expression signature in IPSCs from an FPD-AML patient with correction of RUNX1 mutation to those in OCI-AML5 cells after depletion of RUNX1 by shRNA. (D) OCI-AML5 cells were treated with 1 µM of ARV-825 or OTX015 for 4 hours. RNA-Seq analysis was performed on biologic triplicate RNA samples. mRNAs identified with a fold-change ≥2.0 in either direction (relative to the untreated control) and a P value < .05 in the ARV-825 (1395 down/821 up) and OTX015 (911 down/598 up) treated cells were used to construct a Venn diagram. The Venn diagram shows the expression overlaps between RUNX1 shRNA and treatment with OTX015 or ARV-825.