Mass Cytometry reveals unique phenotypic patterns associated with subclonal diversity and outcomes in multiple myeloma.
Mass Cytometry reveals unique phenotypic patterns associated with subclonal diversity and outcomes in multiple myeloma.
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DOI：
10.1038/s41408-023-00851-5
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发表时间：
2023-05-22
影响因子：
12.8
通讯作者：
Kumar, Shaji K. K.
中科院分区：
文献类型：
--
作者：
Baughn, Linda B. B.;Jessen, Erik;Sharma, Neeraj;Tang, Hongwei;Smadbeck, James B. B.;Long, Mark D. D.;Pearce, Kathryn;Smith, Matthew;Dasari, Surendra;Sachs, Zohar;Linden, Michael A. A.;Cook, Joselle;Stewart, A. Keith;Chesi, Marta;Mitra, Amit;Bergsagel, P. Leif;Van Ness, Brian;Kumar, Shaji K. K.
多发性骨髓瘤（MM）仍然是一种无法治愈的浆细胞（PC）恶性肿瘤。尽管已知MM肿瘤细胞显示出广泛的瘤内遗传异质性，但尚未全面评价肿瘤蛋白质组学图谱。我们使用34种抗体靶点，通过质谱流式细胞术（CyTOF）评估了来自新诊断或复发/难治性MM患者的49份原发性肿瘤样本，以表征单细胞表面和细胞内信号蛋白的整合景观。我们在所有样品中鉴定了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相关。表型元簇1的丰度增加，其特征在于CD45升高和BCL-2表达降低，与良好的治疗反应和改善的总生存率显著相关，与肿瘤遗传异常或患者人口统计学变量无关。我们使用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，并表明亚克隆蛋白质谱可能是临床行为和结果的重要决定因素。
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.
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单细胞 RNA seq 揭示复发性多发性骨髓瘤的克隆多样性和预后基因
影响因子：
10.6
作者：
He H;Li Z;Lu J;Qiang W;Jiang S;Xu Y;Fu W;Zhai X;Zhou L;Qian M;Du J
通讯作者：
Du J
影响因子：
3.5
作者：
Courville, Elizabeth L.;Yohe, Sophia;Linden, Michael A.
通讯作者：
Linden, Michael A.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
影响因子：
20.3
作者：
Keats, Jonathan J.;Chesi, Marta;Bergsagel, P. Leif
通讯作者：
Bergsagel, P. Leif
DOI：
10.3324/haematol.2010.030296
发表时间：
2011-01-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Hose, Dirk;Reme, Thierry;Goldschmidt, Hartmut
通讯作者：
Goldschmidt, Hartmut