Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma
This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.794144/full |
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| author | Jiadai Xu Yue Wang Zheng Wei Jingli Zhuang Jing Li Yifeng Sun Liang Ren Yawen Wang Panpan Li Shiyang Gu Yian Zhang Jifeng Jiang Chen Chen Yu Zhang Peng Liu |
| author_facet | Jiadai Xu Yue Wang Zheng Wei Jingli Zhuang Jing Li Yifeng Sun Liang Ren Yawen Wang Panpan Li Shiyang Gu Yian Zhang Jifeng Jiang Chen Chen Yu Zhang Peng Liu |
| author_sort | Jiadai Xu |
| collection | DOAJ |
| description | This study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM. |
| first_indexed | 2024-12-20T15:36:45Z |
| format | Article |
| id | doaj.art-e6d3c987d395420ca3f2f54999a854ea |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T15:36:45Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-e6d3c987d395420ca3f2f54999a854ea2022-12-21T19:35:23ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.794144794144Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple MyelomaJiadai Xu0Yue Wang1Zheng Wei2Jingli Zhuang3Jing Li4Yifeng Sun5Liang Ren6Yawen Wang7Panpan Li8Shiyang Gu9Yian Zhang10Jifeng Jiang11Chen Chen12Yu Zhang13Peng Liu14Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Hematology, Zhongshan Hospital, Fudan University, Shanghai, ChinaThis study attempted to investigate how clonal structure evolves, along with potential regulatory networks, as a result of multiline therapies in relapsed/refractory multiple myeloma (RRMM). Eight whole exome sequencing (WES) and one single cell RNA sequencing (scRNA-seq) were performed in order to assess dynamic genomic changes in temporal consecutive samples of one RRMM patient from the time of diagnosis to death (about 37 months). The 63-year-old female patient who suffered from MM (P1) had disease progression (PD) nine times from July 2017 [newly diagnosed (ND)] to Aug 2020 (death), and the force to drive branching-pattern evolution of malignant PCs was found to be sustained. The mutant-allele tumor heterogeneity (MATH) and tumor mutation burden (TMB) initially exhibited a downward trend, which was then upward throughout the course of the disease. Various somatic single nucleotide variants (SNVs) that had disappeared after the previous treatment were observed to reappear in later stages. Chromosomal instability (CIN) and homologous recombination deficiency (HRD) scores were observed to be increased during periods of all progression, especially in the period of extramedullary plasmacytoma. Finally, in combination with WES and scRNA-seq of P1-PD9 (the nineth PD), the intro-heterogeneity and gene regulatory networks of MM cells were deciphered. As verified by the overall survival of MM patients in the MMRF CoMMpass and GSE24080 datasets, RUNX3 was identified as a potential driver for RRMM.https://www.frontiersin.org/articles/10.3389/fcell.2021.794144/fullmultiple myelomaclonal evolutionrelapsedrefractoryheterogeneity |
| spellingShingle | Jiadai Xu Yue Wang Zheng Wei Jingli Zhuang Jing Li Yifeng Sun Liang Ren Yawen Wang Panpan Li Shiyang Gu Yian Zhang Jifeng Jiang Chen Chen Yu Zhang Peng Liu Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma Frontiers in Cell and Developmental Biology multiple myeloma clonal evolution relapsed refractory heterogeneity |
| title | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
| title_full | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
| title_fullStr | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
| title_full_unstemmed | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
| title_short | Single-Cell Transcriptomes Combining with Consecutive Genomics Reveal Clonal Evolution and Gene Regulatory Networks in Relapsed and Refractory Multiple Myeloma |
| title_sort | single cell transcriptomes combining with consecutive genomics reveal clonal evolution and gene regulatory networks in relapsed and refractory multiple myeloma |
| topic | multiple myeloma clonal evolution relapsed refractory heterogeneity |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.794144/full |
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