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Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics

ABSTRACT: Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics

PROVIDER: PRJNA1273068 | ENA |

REPOSITORIES: ENA

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Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [mouse]

Project description:Here, we used subcellular spatial transcriptomics to profile the expression of 5,001 genes in human bone marrow in the context of monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma. Using this approach, we explored the plasma cell and stroma ecosystem in bone marrow trephines from 21 individuals including 7 with pre-malignant disease and 10 with active multiple myeloma.

2025-07-14 | GSE299195 | GEO

Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [human]

2025-07-14 | GSE299193 | GEO

Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [mouse]

Project description:Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [mouse]

| PRJNA1273056 | ENA

Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [human]

Project description:Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics [human]

| PRJNA1273065 | ENA

Spatial transcriptomics unveils novel potential disease mechanisms associated with the microenvironment in Multiple Myeloma

Project description:Understanding the spatial organization of the bone marrow (BM) microenvironment at single cell resolution and the niche specific transcriptional regulatory programs remains a challenge. Using formalin-fixed paraffin-embedded (FFPE) samples from our recently described MIcγ1 multiple myeloma (MM) mouse model (Larrayoz et al, Nat Med. 2023), we performed spatial transcriptional profiling of healthy and multiple myeloma BM using the Visium Spatial Gene Expression analysis (10x Genomics). A custom data-analysis framework that combines spatial with single-cell transcriptomic profiles allowed us to identify cell type composition and establish specific cell relations within the bone marrow. As a result, we defined the spatial distribution of transcriptionally heterogenous MM plasma cell (MM-PC) groups. Furthermore, we spatially defined transcriptional programs involved in the pathogenesis of MM within the BM microenvironment that were associated with MM-PC density gradient, such as the spatial location of T cells with effector and exhausted phenotypes. Application of spatial transcriptomics to FFPE human BM biopsies with varying degrees of PC infiltration validated findings from our murine model. The application of spatial transcriptomics to fully mineralized tissues provides a comprehensive spatial overview of the BM microenvironment allowing the identification of deregulated mechanism involved in the pathogenesis of diseases such as MM.

2025-06-09 | GSE269875 | GEO

Spatial transcriptomics based characterization of spatial architecture in human multiple primary lung cancer

Project description:Multiple primary lung cancers (MPLC) pose diagnostic and therapeutic challenges in the clinic. Here, we orchestrated the cellular atlas and spatial architecture of MPLC based on spatial transcriptomics.

2022-04-23 | GSE200916 | GEO

Spatial transcriptomics based characterization of spatial architecture in human multiple primary lung cancer

Project description:Spatial transcriptomics based characterization of spatial architecture in human multiple primary lung cancer

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Serum protein N-glycosylation changes in multiple myeloma

Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>

2022-04-27 | MTBLS676 | MetaboLights

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma

Project description:The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multi-omics analyses of bone marrow-confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary NK and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.

2025-02-10 | GSE284727 | GEO

Profiling the spatial architecture of multiple myeloma in human bone marrow trephines with spatial transcriptomics

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-07-13 | GSE299207 | GEO