Table 2 Summary of single-cell studies in MM
Reference | Sample input | Sample size (n) | Methodology | Major findings |
|---|---|---|---|---|
Ledergor et al. [33] | BM and PB tumor cells from healthy donors (n = 11), MGUS (n = 7), SMM (n = 6), NDMM (n = 12), amyloidosis (n = 4) | 40 | scRNA-seq | Identified inter- and intral-heterogeneity across disease spectrum of MM; detected rare tumour clones at SMM share similar molecular profile with active MM; characteristics of single CTCs reflect the transcriptional status of the matched BMPCs |
Khoo et al. [130] | NA | NA | scRNA-seq | Characterized dormant malignant plasma cells expressing a unique myeloid signature; AXL gene retains myeloma cells in a dormant state |
Zavidij et al. [39] | Immune cells of BM from healthy donors (n = 9), MGUS (n = 5), low-risk SMM (n = 3), high-risk SMM (n = 8), NDMM (n = 7) | 32 | scRNA-seq | Revealed early alterations in immune cell composition and features associated with MM progression |
Liu et al. [37] | Tumor cells and immune cells from paired SMM-NDMM (n = 3), paired NDMM-RRMM (n = 6), NDMM (n = 4), RRMM (n = 1) | 14 | scRNA-seq, WGS/ WES | Longitudinal multi-omic investigation of samples at different disease stages; integrated analysis identified 3 clonal patterns; detected PCs population with B-cell features suggesting PCs origin; targeted protein analyses confirmed differential expression among distinct clusters |
Cohen et al. [131] | Tumor cells from healthy donors (n = 11), NDMM (n = 15), PRMM (n = 41) | 67 | scRNA-seq | Identified expression signatures of patients with primary refractory MM participating in clinical trials correlated with clinical outcomes; Identification of a signature of highly resistant MM and revealed PPIA as a promising therapeutic target |
de Jong et al. [132] | Stromal cells, immune cells and tumor cells from healthy donors (n = 7), NDMM (n = 13) | 20 | scRNA-seq, Bulk RNA-seq | Identified inflammatory mesenchymal stromal cells population with myeloma-specific pattern in BME, which persisted in the BM even after successful antitumor treatment |
Cho et al. [133] | BM and PB sorted NK cells from NDMM (n = 3) | 3 | scRNA-seq, Flow cytometry | Identified a subset of adaptive NK cells with distinct immunophenotypic features and exert substantial cytotoxic activity against myeloma cells in the presence of daratumumab |
Ryu et al. [134] | BM and extramedullary biopsies of MM (n = 15) | 15 | scRNA-seq | Aggressive extramedullary myeloma is associated with transcriptional signatures that support myeloma cell growth and immune evasion |
He et al. [34] | BM CD138+ cells from NDMM (n = 12) and RRMM (n = 6) | 18 | scRNA-seq, scVDJ-seq | Revealed that myeloma cells from most of NDMM and RRMM patients consist of a major clone, and identified several meta-programs and biomarkers correlated with disease progression and relapse of MM |
Frede et al. [36] | Sorted CD138+ and CD45+ cells from healthy donors (n = 2) and RRMM (n = 8) | 10 | scRNA-seq, scATAC-seq | Revealed profound intratumoral heterogeneity and a loss of lineage restriction in myeloma cells from RRMM. Anti-myeloma treatment reduced developmental potential and CXCR4 may serve as a promising target for immunotherapy |
Li et al. [35] | BMMC and PBMC from healthy donors (n = 3) and MM during treatment (n = 10) | 13 | scRNA-seq, Flow cytometry | Identified a subset of ZNF683+ NK cells in MM patients and exhibited an exhausted phenotype by inhibiting EAT-2/SLAMF7 axis |
Merz et al. [135] | BM and osteolytic lesion samples from NDMMÂ (n = 7) and RRMMÂ (n = 3) | 10 | scRNA-seq, WES | Spatially revealed enormous inter- and intra-tumor heterogeneity in both BM and osteolytic lesions, and identified key genes associated with myeloma bone disease |
Tirier et al. [38] | Tumor and immune cells from RRMM (n = 20) during treatment | 20 | scRNA-seq | Demonstrated that 1q + subclones harbored a distinct transcriptional signature and showed frequent expansion during therapy. The BME was shaped towards an immune suppressive status in RRMM via increased expression of inflammatory cytokines and enhanced interaction with the myeloid cell subsets |
Rodriguez-Marquez et al. [136] | anti-BCMA CAR-T cells from MM patients (n = 3) | 3 | scRNA-seq | Identified regulons involved with CARHigh T cells activation and exhaustion, revealing potential mechanisms underlying their differential functionality |
Da Vià et al. [137] | anti-BCMA CAR-T cells from RRMM at baseline and relapse (n = 1) | 1 | scRNA-seq | Identified a selected clone with loss of BCMA acquired by homozygous deletion and provided insights into CAR-T resistance |
Liang et al. [138] | BM aspirates from healthy donor (n = 1), NDMM (n = 3) and RRMM (n = 4) | 8 | scRNA-seq, Nanopore sequencing | Revealed two clonal evolution patterns that related to tumor origins and microenvironment reprogramming |
Masuda et al. [139] | Serial BM aspirates from RRMM (n = 1) | 1 | scRNA-seq | Identified a distinct cell cluster which emerged during lenalidomide treatment and eliminated after PI treatment. Identified a drug-response gene; PELI2, which confers the PI sensitivity and serves as a predictive biomarker |
Jung et al. [140] | BMMCs from NDMM (n = 18) at baseline and after treatment | 18 | scRNA-seq | Identified a 24-gene signature that upregulated in SORs, revealed dysfunctional phenotypes of T cells in SORs, identified three monocytes subsets associated with bortezomib responsiveness |
Yao et al. [141] | BMMCs from NDMM (n = 18) | 18 | scRNA-seq, CyTOF, CITE-seq | CITE-seq showed advantages in distinguishing T-cell subtypes. CD4+ T/CD8+ T cells ratio showed a decrease in MM patients with ISS stage 3 |
Li et al. [142] | BMMCs from MGUS (n = 4), NDMM (n = 5) and RRMM (n = 5) | 14 | scRNA-seq, Flow cytometry, Bulk RNA-seq | Revealed alterations in MM-TME during disease progression and TAM reprogramming, targeting both CD47 and MIF showed potent anti-MM effects |