Fig. 2: Metabolic reprogramming mediates MM cells’ resistance to DNA damage activation.

A Western blot analysis of ILF2, γH2AX, and cleaved caspase 3 in KMS11 cells treated with NT or ILF2 ASOs (0.5 μM) for 1 week (wk; left) or 3 weeks (right). Vinculin was used as a loading control. Every experiment was performed in triplicate (1–3). B Western blot analysis of ILF2, γH2AX, and cleaved caspase 3 in JJN3 cells treated with NT or ILF2 ASOs (1 μM) for 1 week (wk; left) or 3 weeks (right). Vinculin was used as a loading control. Every experiment was performed in triplicate (1–3). C Uniform manifold approximation and projection (UMAP) of scRNA-seq data displaying pooled (n = 2 independent experiments) single JJN3 cells after 3 weeks of NT ASO (n = 7041 cells) or ILF2 ASO (n = 4462 cells) treatment. Different colors represent the cluster (left), sample origin (middle) and the 2 identities of the main clusters (right). Cluster 10 which included basal apoptotic cells was removed from the pathway enrichment analysis shown in Fig. 2D. D Pathway enrichment analysis of the significantly upregulated genes in ILF2 ASO–treated cells compared with NT ASO–treated cells in the major clusters 1 (left) and 2 (right) shown in Fig. 2C (adjusted P ≤ 0.05). The top 10 Reactome gene sets are shown. E Log₂ fold change (FC) of all significant metabolites that were significantly enriched in JJN3 cells treated with ILF2 ASOs for 3 weeks compared with cells treated with NT ASOs (left). The significant metabolites in the tricarboxylic acid cycle pathway (top right, P = 0.016), and the pyrimidine pathway (bottom right, P < 0.001) are highlighted in pink and violet, respectively (right) (n = 2 independent replicates per group; adjusted P ≤ 0.05). A detailed description of the statistical analysis is included in “Methods” section. Source data are provided as a Source Data file.