Single-cell sequencing identifies characteristics of disease and bone marrow in concurrent multiple myeloma and myelodysplastic syndrome

In the current study, we applied single-cell sequencing to the bone marrow cells of four patients with concurrent MM and MDS (MM-MDS) to identify distinct cell type distributions and transcriptome signatures compared to that from MM patients and healthy donors. Despite of heterogeneity, the degree of plasma cell expansion and malignancy in the concurrent patients were inferior than that in MM patients. Additionally, the differentiation of hematopoietic stem cells is incomplete, involving abnormalities in red blood cell differentiation, higher frequency of B cell enrichment accompanying positive regulation of immune response, as well as differences in the pathways and endpoints of myeloid differentiation, leading to the appearance of neutrophil-like monocytes. In MM patients, B cells and stromal cells interact with plasma cells mainly via IL-16/CD4 signaling, however in MM-MDS patients, B cells interact with plasma cells mainly via BTLA-TNFRSF14 signaling and stromal cells via CXCL12-CXCR4 signaling, respectively. Bone marrow aspirates were isolated from four patients diagnosied with concurrent MM and MDS. The scRNA-seq data from 4 healthy donors (HDs) and MM patients were downloaded from the Gene Expression Omnibus database (GSE120221), and healthy donor (n = 4) without MM or MDS disease obtained from GSE189460 served as the control group.