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Fig. 3 | Molecular Cancer

Fig. 3

From: Malignant clonal evolution drives multiple myeloma cellular ecological diversity and microenvironment reprogramming

Fig. 3

Relationship between the malignant progression of MM and the evolution of cell clones. A Gene transcriptional activity of SV event genes in MM malignant subclones. Left: SV spectrum of patients with MM. These SVs occur only in patients with MM, but not in control donors. Right: Expression pattern of SV genes in malignant plasma cell clusters. B CNV atlas of MM patients at the large-volume BM tissue level and at the single-cell level. C Transcriptional activity of CNV event genes in MM malignant subclones. Genes identified to be associated with the development of MM in previous studies have been highlighted. D Transcriptional activity of SNV event genes in MM malignant subclones. The SNV events detected simultaneously by the single-molecule long-read genome sequencing and single-cell transcriptome are demonstrated. Left: SNV mapping of patients with MM at the level of large-volume BM tissue. Middle: SNV atlas of MM patients at the level of BM monocytes. Right: Corresponding SNV gene expression patterns in the malignant plasma cell clusters. E Co-expression modules of transcription factors in malignant subclones of BM from patients with MM. Left: Identification of regulator modules based on the regulator’s CSI matrix. Middle: Representative transcription factors and their binding motifs in the module. Right: association of modules with malignant subclones. F t-SNE single-cell atlas mapping of MM malignant subclone-specific GRN. G RNA rate flow of MM malignant subclones mapped in t-SNE single-cell profiles. H Proposed chronological clonal evolutionary trajectory of MM malignant plasma cells mapped on the t-SNE single-cell atlas. The proportion of NDMM and RRMM cells characterizing the drug sensitivity of malignant cell subclones demonstrated using pie charts. The clonal evolution landscape characterizes the core state of MM malignant subclones in the malignant process with phenotypic transition differentiation. I Expression patterns of genes associated with the proposed chronological clonal evolution of MM malignant plasma cells and their biological signaling and cascade activation. J Structural changes in MM malignant plasma cells. Fish plots demonstrate the structural changes in MM malignant plasma cells from their origin through natural development, drug selection, and eventual relapse. K Global clonal evolutionary patterns of MM malignant plasma cells. Pie chart showing the cell proportion of NDMM and RRMM cells characterizing the drug sensitivity of malignant cell subclones. SV, structural variation; CNV, copy number variations; MM, multiple myeloma; BM, bone marrow; SNV, single nucleotide variation; CSI, connection specificity index; t-SNE, t-distributed stochastic neighbor embedding; GRN, gene regulation network

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