Abstract
Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant plasma cell population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47, and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.
Data availability
Sequencing data have been deposited in GEO under accession code GSE176131.
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Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma.NCBI Gene Expression Omnibus, GSE117156.
Article and author information
Author details
Funding
National Natural Science Foundation of China (Youth Funds,82002212)
- Ling Zhong
Science & Technology Department of Sichuan Province (Applied Basic Research,2022YFS0100)
- Peng Hao
Chengdu Science and Technology Bureau (Applied Basic Research,2019-YF05-00572-SN)
- Ling Zhong
China Postdoctoral Science Foundation (general program，2019M663567)
- Ling Zhong
UESTC (Basic scientific research,ZYGX2020J024)
- Ling Zhong
UESTC (Medicine-engineering interdisciplinary,ZYGX2021YGLH006)
- Ling Zhong
Science &Technology Department of Sichuan Province (Outstanding Youth Fund，2022JDTD0024)
- Bo Gong
Chengdu Science and Technology Bureau (Applied Basic Research,2022-YF05-01625-SN)
- Bo Gong
Sichuan cadre health care project (Sichuan cadre health care project,2022-216)
- Wei Zhang
UESTC (Medicine-engineering interdisciplinary,ZYGX2021YGLH204)
- Wei Zhang
The roles of the funders were to do single cell sequence, analysis data, and verify the conclusions.
Ethics
Human subjects: Written informed consents were obtained from all subjects. All experimental procedures were approved by the Medical ethics committee of Sichuan Provincial People's Hospital and carried out in accordance with the principles of the Declaration of Helsinki. ALL of the patients signed the informed consent containing contact Information, the purpose of the study, risks and benefits from this study, consent to publish the manuscript. The protocol numbers was 2020-240.
Copyright
© 2022, Gong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma
eLife 11:e75340.
https://doi.org/10.7554/eLife.75340
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