Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics

Area of Science:

• Hematology
• Oncology
• Spatial Biology

Background:

• Bone marrow (BM) is a complex tissue where spatial organization influences cell behavior and disease.
• Understanding the spatial context is crucial for dissecting Multiple Myeloma (MM) pathogenesis.

Purpose of the Study:

• To apply spatial transcriptomics to map cellular composition and interactions within the BM microenvironment in MM.
• To characterize the spatial distribution of malignant plasma cells (MM-PC) and their associated gene expression patterns.

Main Methods:

• Utilized Visium Spatial Gene Expression on formalin-fixed paraffin-embedded (FFPE) BM sections from mouse models and MM patients.
• Developed a custom analytical framework integrating spatial and single-cell transcriptomic data.
• Mapped in situ cellular composition and interactions within the BM microenvironment.

Main Results:

• Identified spatially distinct gene programs linked to MM pathogenesis, including NETosis and IL-17 signaling.
• Observed reduced NETosis and IL-17 signaling in MM-PC-rich regions.
• Found a spatial gradient of T cell phenotypes (effector to exhausted) relative to MM-PC proximity, present in patient samples.

Conclusions:

• Spatial transcriptomics with Visium technology is capable of characterizing spatially regulated mechanisms in MM pathogenesis.
• The study highlights the importance of spatial context in MM and identifies specific molecular signatures within the tumor microenvironment.
• Demonstrated the utility of FFPE BM biopsies for spatial analysis in MM patients.