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Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and

Lijun Yao1, Reyka G Jayasinghe1, Brian H Lee2

  • 1Washington University School of Medicine, Saint Louis, Missouri.

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|March 27, 2023
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Summary
This summary is machine-generated.

Comparing single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) in multiple myeloma revealed consistent cell type abundances. This study identified markers associated with rapid disease progression.

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Area of Science:

  • Immunology
  • Oncology
  • Genomics
  • Bioinformatics

Background:

  • The Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project aims to characterize the multiple myeloma immune microenvironment.
  • Single-cell technologies like scRNA-seq, CyTOF, and CITE-seq are crucial for dissecting cellular heterogeneity but require concordance assessment.
  • Understanding measurement concordance among these techniques is vital for reliable immune profiling in multiple myeloma.

Purpose of the Study:

  • To compare the concordance of immune cell measurements using scRNA-seq, CyTOF, and CITE-seq in multiple myeloma bone marrow samples.
  • To identify potential markers associated with rapid progression of multiple myeloma.
  • To evaluate the suitability of different cell type marker genes across various single-cell modalities.

Main Methods:

  • Analysis of bone marrow samples from 18 multiple myeloma patients using scRNA-seq, CyTOF, and CITE-seq.
  • Comparative analysis of cell type abundances and marker gene expression across the three single-cell techniques.
  • Integration of data from multiple assays to identify differences between International Staging System stage 3 patients and others, and between rapid progressors and non-progressors.

Main Results:

  • Relatively consistent cell type abundances were observed across scRNA-seq, CyTOF, and CITE-seq, with notable variations in T cells, macrophages, and monocytes.
  • International Staging System stage 3 patients showed a decreased CD4+ T/CD8+ T cell ratio.
  • Upregulation of RAC2 and PSMB9 in natural killer cells was observed in rapid progressors compared to non-progressors, as detected by both scRNA-seq and CITE-seq.

Conclusions:

  • The study provides a comprehensive comparison of three major single-cell technologies for immune profiling in multiple myeloma.
  • Choosing appropriate cell type marker genes is crucial for accurate analysis across different single-cell modalities.
  • Specific molecular markers, including RAC2 and PSMB9 in natural killer cells, are associated with multiple myeloma rapid progression and warrant further investigation.