Fig. 1

Single-cell atlas of myeloma progression pinpoints PRKD2 as a stage-linked hub. (A) UMAP coloured by 20 clusters; split panels show stages. Dashed circle highlights the plasma-cell region where an “MM-malignant plasma” cluster emerges in MGUS and expands through SMM to dominate MM. HD (n = 5), MGUS (n = 6), SMM (n = 4) and MM (n = 4). (B) Bar chart of mean cell-type frequencies per stage. (*P < 0.05, compared with HD) (C) Heat-map of normal plasma-cell DEGs; PRKD2 (red) rises stepwise HD→MM. Heat-map was drawn in R [v4.3.3] using ComplexHeatmap [v2.1] (Bioconductor; https://bioconductor.org/packages/ComplexHeatmap) from vst-normalized expression with per-gene z-scores. (D) Heat-map for MM-malignant plasma cells, showing further PRKD2 up-regulation plus stress/immune-evasion genes. Generated in R [v4.3.3] with ComplexHeatmap [v2.1] as in (C). (E) Box-scatter plots of mRNAsi and EREG_mRNAsi in bulk plasma cells (****P < 0.0001, Wilcoxon). (F) Same indices within the MM-malignant subset. (G) Feature-density UMAPs: PRKD2 signal (yellow) intensifies from HD to MM within plasma cells. (H–K) PRKD2 expression correlates with mRNAsi and EREG_mRNAsi; Points are coloured by clinical group (HD, MGUS, SMM, MM). Separate solid lines represent group-specific linear regressions with 95% confidence ribbons. An ANCOVA comparing the four slopes yields a significant group × PRKD2 interaction (F = 4.89, p = 0.003), indicating that the relationship between PRKD2 expression and stemness indices differs across disease stages. (L) iTALK network linking CD4⁺, CD8⁺, NK/NKT, normal and malignant plasma cells in MM; arrow width ∝ ligand–receptor counts. (M) Chord diagram of dominant MM-plasma/NK→CD4⁺ T signals; VCAN, HSP90B1, RNASE2 and HRAS target TLR2. PRKD2 expression in sending plasma cells scales with total TLR2 engagement.