TY - JOUR
T1 - Single cell clonotypic and transcriptional evolution of multiple myeloma precursor disease
AU - Dang, Minghao
AU - Wang, Ruiping
AU - Lee, Hans C.
AU - Patel, Krina K.
AU - Becnel, Melody R.
AU - Han, Guangchun
AU - Thomas, Sheeba K.
AU - Hao, Dapeng
AU - Chu, Yanshuo
AU - Weber, Donna M.
AU - Lin, Pei
AU - Lutter-Berka, Zuzana
AU - Berrios Nolasco, David A.
AU - Huang, Mei
AU - Bansal, Hima
AU - Song, Xingzhi
AU - Zhang, Jianhua
AU - Futreal, Andrew
AU - Moreno Rueda, Luz Yurany
AU - Symer, David E.
AU - Green, Michael R.
AU - Rojas Hernandez, Cristhiam M.
AU - Kroll, Michael
AU - Afshar-Khargan, Vahid
AU - Ndacayisaba, Libere J.
AU - Kuhn, Peter
AU - Neelapu, Sattva S.
AU - Orlowski, Robert Z.
AU - Wang, Linghua
AU - Manasanch, Elisabet E.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/6/12
Y1 - 2023/6/12
N2 - 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.
AB - 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.
KW - hyperdiploid
KW - intra-tumoral heterogeneity
KW - monoclonal gammopathy of undetermined significance
KW - multiple myeloma
KW - non-hyperdiploid
KW - single-cell B cell receptor sequencing
KW - single-cell RNA sequencing
KW - smoldering multiple myeloma
KW - tumor evolution
KW - tumor microenvironment
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U2 - 10.1016/j.ccell.2023.05.007
DO - 10.1016/j.ccell.2023.05.007
M3 - Article
C2 - 37311413
AN - SCOPUS:85161621068
SN - 1535-6108
VL - 41
SP - 1032-1047.e4
JO - Cancer cell
JF - Cancer cell
IS - 6
ER -