FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

Enitociclib treatment confers a robust shift in transcriptional activity in MYC+ DLBCL cell lines. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after 4 hours pretreatment of DLBLC cell lines with three CDK9 inhibitors with unsupervised hierarchical clustering based on 250 nmol/L enitociclib treatment. Heat map showing gene intensity per sample relative to the average level across all samples. Individual genes are shown on the Y axis while samples are shown along the X axis. Red and blue cells correspond to higher and lower RNA-seq levels, respectively after 4 hours of treatment. B, List of top DEGs for each treatment ranked by Padj (cutoff 10–7) with overlapping DEGs as indicated by color coding. C, Significant DEGs were analyzed for enrichment of Reactome pathway membership using a hypergeometric test by mapping genes to genes (if appropriate) for each treatment condition and for KB-0742 treated cells, the Padj value cutoff for the pathway of 10–7 was selected for graphical representation because there were 182 significant pathways (30 shown). The three top pathways for enitociclib and atuveciclib are shown for KB-0742 but the Padj values do not meet the cutoff but are included for comparative purposes.