Fig. 2: Malignant plasma cells frequently persist during long-term survival and display a stable transcriptional phenotype.

a UMAP embedding of the BM plasma cell (PC) compartment colored by the patient. b PC fraction of total BM cells summarized by the patient and compared between clinical groups (Healthy (n = 3), ID (n = 10), LTS (n = 10)). Dots indicate the PC fraction of total BM cells for each sample. Significance was tested by a two-sided unpaired Wilcoxon rank sum test. c Split UMAP of PCs by clinical groups (ID, LTS) highlighting their malignancy annotation (healthy, malignant) derived from inferCNV. The remaining cells are grayed out. d PC UMAP highlighting the dominant immunoglobulin light chain expression. e Representative scatter plots of immunoglobulin expression (highest lambda chain (IGLC) and kappa chain (IGKC)) of healthy (green) and malignant (violet) PCs. f Malignancy score (malignant PC fraction of total PCs) per patient at ID and LTS (n = 9). Large dots indicate the malignant PC fraction of total BM cells for each sample. Significance was tested by a two-sided paired Wilcoxon signed rank test. g Correlation of malignancy score from flow cytometry MRD (number of Light Chain restricted plasma cells/all plasma cells) with malignancy score from inferCNV analysis (number of malignant cells/all plasma cells). Spearman’s Rho and the significance level of correlation are indicated using a two-sided test based on the t distribution. h Euclidean distance of malignant plasma cells between ID and LTS within patients (n = 7) compared to the Euclidean distance of malignant plasma cells at ID and respective nearest neighbor. Patients with less than 2 cells per clinical state were excluded. Significance was tested by a one-sided paired Wilcoxon signed rank test. i Heatmap showing average expression patterns (module scores; scaled by row) of known bulk RNA signatures (Broyl et al. 2010) per patient and clinical state. If not stated otherwise, paired human BM samples from 11 MM patients at ID and LTS, as well as 3 healthy, age-matched controls, were used for comparison. Abbreviations: PC: plasma cells; ID: initial diagnosis; LTS: long-term survival; IGLC: immunoglobulin light chain; LC: lambda chain; KC: kappa chain. Box plots: center line, median; box limits, first and third quartile; whiskers, smallest/largest value no further than 1.5*IQR from the corresponding hinge.