Ingenuity pathway analysis and GSEA in MSC from patients with MGUS, SMM and MM revealed a unique genetic signature in MSC transition. (A) Table overview of unique differentially expressed genes from DESeq2 output such as MAPK7, SPP1 or FGF11 in MGUS MSC, CCND2, WNT7B or SESN2 in SMM MSC as well as several CDK's, MAPK14 or BMP2K in MM MSC within the comparison of all 3 groups (FDR q-value ≤0.05). (B) Ingenuity pathway analysis predicted the top 5 most probable upstream regulators in MGUS, SMM and MM MSC. (C) GSEA contrasting healthy samples to MGUS, SMM and MM samples. The results confirmed a strong enrichment for the BMP/TGFB-signaling pathway signature. Neither TNFA/NFKB nor WNT are strongly enriched. MM MSC to healthy MSC confirmed a strong enrichment of a gene set also for TNF/p38 and Estrogen signaling signature. For all plots, the normalized enrichment score, P-values and (FDR q-value) are given.