Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)
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 pat...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/75340 |
| _version_ | 1797983590037848064 |
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| author | Ling Zhong Peng Hao Qian Zhang Tao Jiang Huan Li Jialing Xiao Chenglong Li Lan Luo Chunbao Xie Jiang Hu Liang Wang Yuping Liu Yi Shi Wei Zhang Bo Gong |
| author_facet | Ling Zhong Peng Hao Qian Zhang Tao Jiang Huan Li Jialing Xiao Chenglong Li Lan Luo Chunbao Xie Jiang Hu Liang Wang Yuping Liu Yi Shi Wei Zhang Bo Gong |
| author_sort | Ling Zhong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:49:42Z |
| format | Article |
| id | doaj.art-f4c2777e3f3c4d229ed3d4d8a2cc29b0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T06:49:42Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f4c2777e3f3c4d229ed3d4d8a2cc29b02022-12-22T04:39:16ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.75340Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM)Ling Zhong0Peng Hao1Qian Zhang2Tao Jiang3Huan Li4https://orcid.org/0000-0001-6624-9755Jialing Xiao5Chenglong Li6Lan Luo7Chunbao Xie8Jiang Hu9Liang Wang10Yuping Liu11Yi Shi12Wei Zhang13Bo Gong14https://orcid.org/0000-0003-2763-6829Department of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, ChinaDepartment of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of hematology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of hematology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaChengdu University of Traditional Chinese Medicine, Chengdu, ChinaThe Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Orthopaedics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Health Management, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China; The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaMultiple 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.https://elifesciences.org/articles/75340multiple myelomaRevised International Staging SystemNKG7RRM2EBV infectionR-ISS |
| spellingShingle | Ling Zhong Peng Hao Qian Zhang Tao Jiang Huan Li Jialing Xiao Chenglong Li Lan Luo Chunbao Xie Jiang Hu Liang Wang Yuping Liu Yi Shi Wei Zhang Bo Gong Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) eLife multiple myeloma Revised International Staging System NKG7 RRM2 EBV infection R-ISS |
| title | Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) |
| title_full | Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) |
| title_fullStr | Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) |
| title_full_unstemmed | Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) |
| title_short | Revised International Staging System (R-ISS) stage-dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma (MM) |
| title_sort | revised international staging system r iss stage dependent analysis uncovers oncogenes and potential immunotherapeutic targets in multiple myeloma mm |
| topic | multiple myeloma Revised International Staging System NKG7 RRM2 EBV infection R-ISS |
| url | https://elifesciences.org/articles/75340 |
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