Identification of immune reconstitution and hematopoiesis restoration in bone marrow of multiple myeloma patients with high-dose melphalan following auto-HSCT by scRNA-seq

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal expansion of plasma cells in the bone marrow (BM). The high-dose chemotherapy following autologous hematopoietic stem cell transplantation (auto-HSCT) is a mainstay therapy for MM. However, effect of therapy on reconstitution of both immune and hematopoietic stem and progenitor cell (HSPCs) in BM of MM patients is pooly understood. In this study, we investigated the significance of that using single-cell RNA sequencing (scRNA-seq). The scRNA-seq data of bone marrow mononuclear cells (BMMCs) from three MM patients with high-dose melphalan following auto-HSCT were integrated these data with scRNA-seq profiles from three newly diagnosed MM patients and three healthy donors. Our data showed that the malignant plasma cells in BM were strongly reduced to 0.09% in the MM group with therapy relative to 22.03% in control MM group. Notably, the proportions of pre-B cells, T cells, natural killer (NK) cells, and HSPCs were significantly elevated to 0.97%, 61.01%, 10.81% and 2.32% in BM of MM groupwith therapy relative to 0.10%, 27.34%, 7.17% and 0.46% in control MM group, indicating a robust reconstitution of both immune and HSPCs. The transcriptional landscape of HSPCs demonstrated functional restoration, with the enrichment of pathways involved in immune activation and multilineage differentiation. Pseudotime analysis revealed the distinct plasma cell trajectories and a notable downregulation of the unfolded protein response (UPR) pathway following by the treatment. Our findings provide a new insight into the comprehensive understanding of single-cell atlas in BM of MM by the therapy.