美国德克萨斯大学MD安德森癌症中心Elisabet E. Manasanch和Linghua Wang共同合作，近期取得重要工作进展。他们研究发现了多发性骨髓瘤前体疾病的单细胞克隆型和转录演化。相关研究成果2023年6月12日在线发表于《癌细胞》杂志上。

据介绍，多发性骨髓瘤仍然是一种无法治愈的疾病，并且尚未完全了解前体疾病（包括意义未明的单克隆丙种球蛋白病和冒烟型多发性骨髓瘤）的细胞和分子演化。

研究人员将52名骨髓瘤前体患者的单细胞RNA和B细胞受体测序数据与骨髓瘤和正常供体进行了比较。综合分析数据揭示了超二倍体与非超二倍体样本中恶性转化的早期基因组驱动因素、不同的转录特征和不同的克隆扩增。

此外，研究人员观察了具有潜在治疗意义的患者内部异质性，并确定了从骨髓瘤前体疾病到骨髓瘤的不同演化模式。研究人员还证明了与骨髓瘤细胞中特定基因组变化相关微环境的独特特征。

总之，这些发现增加了人们对骨髓瘤前体疾病进展的了解，为患者风险分层、生物标志物发现和可能的临床应用提供了有价值的见解。

附：英文原文

Title: Single cell clonotypic and transcriptional evolution of multiple myeloma precursor disease

Author: 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

Issue&Volume: 2023/06/12

Abstract: Multiple myeloma remains an incurable disease, and the cellular and molecular evolutionfrom precursor conditions, including monoclonal gammopathy of undetermined significanceand smoldering multiple myeloma, is incompletely understood. Here, we combine single-cellRNA and B cell receptor sequencing from fifty-two patients with myeloma precursorsin comparison with myeloma and normal donors. Our comprehensive analysis reveals earlygenomic drivers of malignant transformation, distinct transcriptional features, anddivergent clonal expansion in hyperdiploid versus non-hyperdiploid samples. Additionally,we observe intra-patient heterogeneity with potential therapeutic implications andidentify distinct patterns of evolution from myeloma precursor disease to myeloma.We also demonstrate distinctive characteristics of the microenvironment associatedwith specific genomic changes in myeloma cells. These findings add to our knowledgeabout myeloma precursor disease progression, providing valuable insights into patientrisk stratification, biomarker discovery, and possible clinical applications.

DOI: 10.1016/j.ccell.2023.05.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00174-5