文章：

一种用于原代人急性髓系白血病标本中有效联合疗法鉴定的新方法

A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens

原文发布日期：2017-02-17

DOI: 10.1038/bcj.2017.10

类型: Original Article

开放获取: 是

英文摘要：

Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations. Initially conducted with a selected library of 5000 small molecules and 20 primary AML specimens, it reveals 5 broad classes of sensitized therapeutic target pathways along with their synergistic patient-specific fingerprints. This novel method opens new avenues for the development of AML personalized therapeutics and may be generalized to other tumor types, for which in vitro cancer stem cell cultures have been developed.

摘要翻译： 

迄今为止，仍缺乏适用于原发性白血病样本研究的合适培养方法，且现有的化合物筛选方案难以适应大规模协同药物组合研究。本研究报道了一种新策略，能有效筛选出对原代人急性髓系白血病样本具有活性的小分子之间的合成致死相互作用。在单次给药实验及保留白血病干细胞活性的培养条件下，该策略大幅减少了识别有前景化合物组合所需的试验次数。通过初步使用精选的5000种小分子化合物库及20例原代急性髓系白血病样本，研究揭示了5大类敏感化治疗靶点通路及其协同作用的患者特异性指纹图谱。这一新方法为开发急性髓系白血病个性化疗法开辟了新途径，并有望推广至其他已建立体外癌干细胞培养体系的肿瘤类型。

原文链接：

A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens