Fig. 4

Multi-omics anomaly procedure for MM malignant origin. A Expression pattern characteristics of MM malignant origin. The bottom heatmap shows the expression pattern of type I and IX malignant progenitor marker genes, while the top annotations represent the GSVA score, cell cycle score, and tumor stemness score of type I and IX malignant origin. B Verification and typing of malignant origins in a large-scale clinical MM patient cohort. Top: malignant origin advantage score of the MM clinical patient cohort. The yellow bar represents the type I origin advantage and the blue bar represents the type IX origin advantage. Middle: abundance score of type I and type IX malignant progenitor cells in the clinical patient cohort of MM. The advantage score of malignant origin at the top = type I malignant progenitor cell abundance score - type IX malignant progenitor cell abundance score. Bottom: expression patterns of type I and type IX malignant progenitor marker genes in the MM clinical patient cohort. C Clinical prognostic value of MM malignant origin. Survival curves demonstrating the survival prognostic potential (OS and RFS) of type I and IX malignant progenitor abundance score, malignant origin predominance score, and malignant origin predominance typing in a cohort of patients with MM. D Variation in the malignant origin of MM drives a global gene expression regulatory network. The associated genes were regulated by GRN, SNV, and CNV, and clustered into four modules based on expression correlation to activate or inhibit seven biological signaling pathways. E Molecular mechanism of malignant origin mediated by early carcinogenic drivers. F Expression patterns of immune checkpoints PD-1, PD-L1, and CTLA4 in malignant plasma cells and tumor microenvironment cells in patients with MM. The negative expression of immune checkpoint-related genes in malignant plasma cells and tumor microenvironment cells provides molecular insight at the single-cell level for the poor efficacy of immune checkpoint blocker therapy. G Expression pattern of antitumor immune response cascade-related genes in microenvironment cells. H Communication network with high confidence between early malignant progenitor cells and tumor microenvironment cells in patients with MM. The Circos diagram illustrates each high-confidence ligand-receptor interaction of type I and type IX malignant progenitor cells and microenvironment cells. The direction arrow is from the ligand of the source cell to the receptor of the target cell, and the thickness of the arrow represents the average expression level of the ligand-receptor interaction. I Immune escape mechanism of early malignant progenitor cells in MM. MM, multiple myeloma; GRN, gene regulation network; CNV, copy number variation; SNV, single nucleotide variation; OS, overall survival; RFs, relapse-free survival