The role of proliferating stem‐like plasma cells in relapsed or refractory multiple myeloma: Insights from single‐cell RNA sequencing and proteomic analysis

Summary The management and comprehension of relapsed or refractory multiple myeloma (RRMM) continues to pose a significant challenge. By integrating single‐cell RNA sequencing (scRNA‐seq) data of 15 patients with plasma cell disorders (PCDs) and proteomic data obtained from mass spectrometry‐based analysis of CD138 + plasma cells (PCs) from 144 PCDs patients, we identified a state of malignant PCs characterized by high stemness score and increased proliferation originating from RRMM. This state has been designated as proliferating stem‐like plasma cells (PSPCs). NUCKS1 was identified as the gene marker representing the stemness of PSPCs. Comparison of differentially expressed genes among various PC states revealed a significant elevation in LGALS1 expression in PSPCs. Survival analysis on the MMRF CoMMpass dataset and GSE24080 dataset established LGALS1 as a gene associated with unfavourable prognostic implications for multiple myeloma. Ultimately, we discovered three specific ligand–receptor pairs within the midkine (MDK) signalling pathway network that play distinct roles in facilitating efficient cellular communication between PSPCs and the surrounding microenvironment cells. These insights have the potential to contribute to the understanding of molecular mechanism and the development of therapeutic strategies involving the application of stem‐like cells in RRMM treatment.