AK2 suppression induces DNA damage response in NSD2-overexpressing MM cells. (A) Volcano plots showing genes differentially expressed between AK2-depleted (shAK2) and control (shSc) NTKO and TKO MM cells plotted from RNA-seq data. FC: fold change shAK2/shSc. FDR: false discovery rate. (B) Area proportional Venn diagram of genes upregulated by AK2 suppression in NTKO and TKO MM cells plotted from RNA-seq data. (C) EnrichR pathway analysis of genes upregulated by AK2 suppression in NTKO cells. (D) Heatmaps of genes involved in DNA damage response and cytosolic DNA sensing plotted from RNAseq data of AK2-suppressed NTKO and TKO cells. (E-F) Immunoblot analysis showing protein PARylation in control and AK2-depleted KMS11 NTKO and TKO (E) or parental and NSD2-deficient KMS34 (F) isogenic cells. (G-H) Immunoblot analysis of basal levels of H2AX phosphorylation and cleaved PARP in control and AK2-depleted KMS11 NTKO and TKO (G) or parental and NSD2-deficient KMS34 (H) isogenic cells. Three independent experiments were performed 72 hours after transduction with the indicated shRNA constructs. ∗P <. 05.