Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)

Ling Zhong(University of Electronic Science and Technology of China), Hao Peng(University of Electronic Science and Technology of China), Qian Zhang(University of Electronic Science and Technology of China), Tao Jiang(University of Electronic Science and Technology of China), Huan Li(University of Electronic Science and Technology of China), Jialing Xiao(University of Electronic Science and Technology of China), Chenglong Li(University of Electronic Science and Technology of China), Lan Luo(Chengdu University of Traditional Chinese Medicine), Chunbao Xie(University of Electronic Science and Technology of China), Jiangping Hu(University of Electronic Science and Technology of China), Liang Wang(University of Electronic Science and Technology of China), Yuping Liu(University of Electronic Science and Technology of China), Yi Shi(University of Electronic Science and Technology of China), Wei Zhang(University of Electronic Science and Technology of China), Bo Gong(University of Electronic Science and Technology of China)
eLife
October 25, 2022
10.7554/elife.75340
Cited by 18Open Access
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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 PC 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.

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