PAK1 inhibition leads to leukemic cell death by downregulation of MYC and a MYC transcriptional network. (A) Gene Set Enrichment Analysis of genes expressed differently in IPA-3 (6 μg/mL) or FRAX-597 (2 μg/mL) treated THP-1 cells compared with DMSO. (B) Ingenuity Pathway Analysis-generated image showing the downregulation of genes from the MYC network following treatment with either IPA-3 (6 μg/mL) or FRAX-597 (2 μg/mL). Intensities indicate degree of up- or downregulation. (C) Western blot shows reduction of MYC protein levels after 4 hours of treatment with IPA-3 or FRAX-597 in THP-1 cells. Concentrations shown are micrograms per milliliter. (D) qPCR validation of downregulated MYC network genes after treatment of THP-1 cells with either DMSO, IPA-3 (6 μg/mL) or FRAX-597 (2 μg/mL). (E) qPCR validation of downregulated MYC network genes after knockdown of PAK1 in THP-1 AML cells.