Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Blood Cancer J. 2023 May 22;13(1):84. doi: 10.1038/s41408-023-00851-5.
Multiple myeloma (MM) remains an incurable plasma cell (PC) malignancy. Although it is known that MM tumor cells display extensive intratumoral genetic heterogeneity, an integrated map of the tumor proteomic landscape has not been comprehensively evaluated. We evaluated 49 primary tumor samples from newly diagnosed or relapsed/refractory MM patients by mass cytometry (CyTOF) using 34 antibody targets to characterize the integrated landscape of single-cell cell surface and intracellular signaling proteins. We identified 13 phenotypic meta-clusters across all samples. The abundance of each phenotypic meta-cluster was compared to patient age, sex, treatment response, tumor genetic abnormalities and overall survival. Relative abundance of several of these phenotypic meta-clusters were associated with disease subtypes and clinical behavior. Increased abundance of phenotypic meta-cluster 1, characterized by elevated CD45 and reduced BCL-2 expression, was significantly associated with a favorable treatment response and improved overall survival independent of tumor genetic abnormalities or patient demographic variables. We validated this association using an unrelated gene expression dataset. This study represents the first, large-scale, single-cell protein atlas of primary MM tumors and demonstrates that subclonal protein profiling may be an important determinant of clinical behavior and outcome.
多发性骨髓瘤（MM）仍然是一种无法治愈的浆细胞瘤（PC）恶性肿瘤。虽然已知 MM 肿瘤细胞显示出广泛的肿瘤内遗传异质性，但肿瘤蛋白质组景观的综合图谱尚未得到全面评估。我们通过质谱流式细胞术（CyTOF）使用 34 种抗体靶标对 49 个新诊断或复发/难治性 MM 患者的原发性肿瘤样本进行了评估，以表征单细胞表面和细胞内信号蛋白的综合景观。我们在所有样本中鉴定了 13 个表型元簇。将每个表型元簇的丰度与患者年龄、性别、治疗反应、肿瘤遗传异常和总生存期进行了比较。这些表型元簇中的几个的相对丰度与疾病亚型和临床行为有关。表型元簇 1 的丰度增加，其特征是 CD45 升高和 BCL-2 表达降低，与治疗反应良好和总生存期改善独立于肿瘤遗传异常或患者人口统计学变量显著相关。我们使用一个不相关的基因表达数据集验证了这种关联。这项研究代表了原发性 MM 肿瘤的第一个大规模单细胞蛋白质图谱，表明亚克隆蛋白谱可能是临床行为和结果的重要决定因素。
