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通过单细胞质量累积测定多发性骨髓瘤的治疗敏感性。

Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation.

机构信息

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St., Cambridge, MA, 02139, USA.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215, USA.

出版信息

Nat Commun. 2017 Nov 20;8(1):1613. doi: 10.1038/s41467-017-01593-2.

Abstract

Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are of great interest. Here we utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring their mass accumulation rate (MAR). We show that MAR accurately and rapidly defines therapeutic susceptibility across human multiple myeloma cell lines to a gamut of standard-of-care therapies. Finally, we demonstrate that our MAR assay, without the need for extended culture ex vivo, correctly defines the response of nine patients to standard-of-care drugs according to their clinical diagnoses. This data highlights the MAR assay in both research and clinical applications as a promising tool for predicting therapeutic response using clinical samples.

摘要

多发性骨髓瘤(MM)受益于治疗方面的重大进展,这些进展改善了疗效并降低了发病率。然而,该疾病仍然无法治愈,其特征是耐药性和复发率高。因此,选择最有效的治疗方法的方法引起了极大的关注。在这里,我们利用一种基于测量其质量积累率(MAR)的功能测定法来评估单个多发性骨髓瘤细胞的体外药物敏感性。我们表明,MAR 准确且快速地定义了针对一系列标准治疗方法的人类多发性骨髓瘤细胞系的治疗敏感性。最后,我们证明,我们的 MAR 测定法无需进行体外延长培养,即可根据其临床诊断正确定义九名患者对标准治疗药物的反应。该数据突出了 MAR 测定法在研究和临床应用中的潜力,它是一种使用临床样本预测治疗反应的有前途的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/085e/5694762/2008856fd745/41467_2017_1593_Fig1_HTML.jpg

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