ArticleExperimental & molecular medicine2022
Single-cell analysis of multiple myelomas refines the molecular features of bortezomib treatment responsiveness.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- miR-1248 enhances bortezomib-induced autophagy by targeting MEF2C/p38-MAPK signaling in multiple myeloma.Frontiers in oncology · 2026Article
- Inhibition of CDC27 O-GlcNAcylation coordinates the antitumor efficacy in multiple myeloma through the autophagy-lysosome pathway.Acta pharmacologica Sinica · 2025Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
- T cell phenotype and clonality changes in myeloma patients with short overall survival.JCI insight · 2025Article
- A single-cell transcriptomic atlas of immune cells in Wilson disease identifies copper-specific immune regulation.iScience · 2025Article
- Exploring secondary extramedullary myeloma disease: a five-predictor scoring system with spotlight on double-hit cytogenetics.BMC medicine · 2025Article
- Construction of a treatment response prediction model for multiple myeloma based on multi-omics and machine learning.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?Annals of hematology · 2025Review
- The Sensitive Genes for Cervical Cancer: Two-Sample Mendelian Randomization with Experimental Validation.International journal of women's health · 2025Article
- Single-cell profiling uncovers PTPRG-driven stemness in malignant plasma cells and signatures of treatment failure in multiple myeloma.Frontiers in immunology · 2025Article
- Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics.Clinical & experimental metastasis · 2024Review
- TRIM44, a Novel Prognostic Marker, Supports the Survival of Proteasome-Resistant Multiple Myeloma Cells.Cells · 2024Article
- Targeting the ribosome to treat multiple myeloma.Molecular therapy. Oncology · 2024Article
- MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5.Molecular biology reports · 2024Article
- Natural products targeting the MAPK-signaling pathway in cancer: overview.Journal of cancer research and clinical oncology · 2024Review
- Single-cell technologies in multiple myeloma: new insights into disease pathogenesis and translational implications.Biomarker research · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both the tumor and tumor microenvironment (TME) are crucial for pathogenesis and chemotherapy resistance in multiple myeloma (MM). Bortezomib, commonly used for MM treatment, works on both MM and TME cells, but innate and acquired resistance easily develop. By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 18 treatment-naïve MM patients who later received bortezomib-based treatments. Twelve plasma and TME cell types and their subsets were identified. Suboptimal responders (SORs) to bortezomib exhibited higher copy number alteration burdens than optimal responders (ORs). Forty-four differentially expressed genes for SORs based on scRNA-seq data were further analyzed in an independent cohort of 90 treatment-naïve MMs, where 24 genes were validated. A combined model of three clinical variables (older age, low absolute lymphocyte count, and no autologous stem cell transplantation) and 24 genes was associated with bortezomib responsiveness and poor prognosis. In T cells, cytotoxic memory, proliferating, and dysfunctional subsets were significantly enriched in SORs. Moreover, we identified three monocyte subsets associated with bortezomib responsiveness and an MM-specific NK cell trajectory that ended with an MM-specific subset. scRNA-seq predicted the interaction of the GAS6-MERTK, ALCAM-CD6, and BAG6-NCR gene networks. Of note, tumor cells from ORs and SORs were the most prominent sources of ALCAM on effector T cells and BAG6 on NK cells, respectively. Our results indicate that the complicated compositional and molecular changes of both tumor and immune cells in the bone marrow (BM) milieu are important in the development and acquisition of resistance to bortezomib-based treatment of MM.
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