Genetic interrogation of circulating multiple myeloma cells at single-cell resolution.
Genetic interrogation of circulating multiple myeloma cells at single-cell resolution.
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DOI：
10.1126/scitranslmed.aac7037
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发表时间：
2016-11-02
影响因子：
17.1
通讯作者：
Golub TR
中科院分区：
文献类型：
--
作者：
Lohr JG;Kim S;Gould J;Knoechel B;Drier Y;Cotton MJ;Gray D;Birrer N;Wong B;Ha G;Zhang CZ;Guo G;Meyerson M;Yee AJ;Boehm JS;Raje N;Golub TR
多发性骨髓瘤（MM）仍然是一种无法治愈的疾病，所有患者最终都会出现治疗难治性状态。MM的恒定克隆进化和遗传异质性是耐药疾病出现的可能解释。不幸的是，通过连续骨髓活检监测治疗中的MM基因组演变是不切实际的，因为它涉及侵入性的、痛苦的程序。在这里，我们描述了如何从外周血中以单细胞分辨率非侵入性和高灵敏度分离和表征循环肿瘤细胞（CTC）概括骨髓中的MM。我们证明CTC提供与骨髓MM细胞相同的遗传信息，甚至在某些情况下比骨髓活检更敏感地揭示突变。单个CTC RNA测序能够对MM进行分类并定量评估与预后相关的基因。我们建议将CTC的基因组特征纳入临床试验，以跟踪MM治疗后耐药亚克隆的出现。
Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive, painful procedure. Here, we describe how non-invasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single cell resolution recapitulates MM in the bone marrow. We demonstrate that CTCs provide the same genetic information as bone marrow MM cells, and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.