Single cell clonotypic and transcriptional evolution of multiple myeloma precursor disease.
Minghao Dang, Ruiping Wang, Hans C Lee, Krina K Patel, Melody R Becnel, Guangchun Han, Sheeba K Thomas, Dapeng Hao, Yanshuo Chu, Donna M Weber, Pei Lin, Zuzana Lutter-Berka, David A Berrios Nolasco, Mei Huang, Hima Bansal, Xingzhi Song, Jianhua Zhang, Andrew Futreal, Luz Yurany Moreno Rueda, David E Symer, Michael R Green, Cristhiam M Rojas Hernandez, Michael Kroll, Vahid Afshar-Khargan, Libere J Ndacayisaba, Peter Kuhn, Sattva S Neelapu, Robert Z Orlowski, Linghua Wang, Elisabet E Manasanch
Author Information
Minghao Dang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ruiping Wang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hans C Lee: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Krina K Patel: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Melody R Becnel: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guangchun Han: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sheeba K Thomas: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Dapeng Hao: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yanshuo Chu: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Donna M Weber: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pei Lin: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zuzana Lutter-Berka: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David A Berrios Nolasco: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mei Huang: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hima Bansal: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xingzhi Song: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jianhua Zhang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Andrew Futreal: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Luz Yurany Moreno Rueda: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David E Symer: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael R Green: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cristhiam M Rojas Hernandez: Department of Internal Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael Kroll: Department of Internal Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vahid Afshar-Khargan: Department of Internal Medicine, Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Libere J Ndacayisaba: University of Southern California, Los Angeles, CA, USA.
Peter Kuhn: University of Southern California, Los Angeles, CA, USA.
Sattva S Neelapu: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Robert Z Orlowski: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Linghua Wang: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address: lwang22@mdanderson.org.
Elisabet E Manasanch: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: eemanasanch@mdanderson.org.
Multiple myeloma remains an incurable disease, and the cellular and molecular evolution from precursor conditions, including monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, is incompletely understood. Here, we combine single-cell RNA and B cell receptor sequencing from fifty-two patients with myeloma precursors in comparison with myeloma and normal donors. Our comprehensive analysis reveals early genomic drivers of malignant transformation, distinct transcriptional features, and divergent clonal expansion in hyperdiploid versus non-hyperdiploid samples. Additionally, we observe intra-patient heterogeneity with potential therapeutic implications and identify distinct patterns of evolution from myeloma precursor disease to myeloma. We also demonstrate distinctive characteristics of the microenvironment associated with specific genomic changes in myeloma cells. These findings add to our knowledge about myeloma precursor disease progression, providing valuable insights into patient risk stratification, biomarker discovery, and possible clinical applications.
