文章：

来自高通量药物敏感性和耐药性检测的急变期慢性髓系白血病新候选药物

Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing

原文发布日期：2015-05-01

DOI: 10.1038/bcj.2015.30

类型: Original Article

开放获取: 是

英文摘要：

Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.

摘要翻译： 

尽管酪氨酸激酶抑制剂（TKI）疗法已被引入并取得进展，急变期慢性粒细胞白血病（CML BC）的治疗仍具挑战性。本研究旨在通过采用无偏倚的高通量药物测试平台，为CML BC寻找新的候选药物。我们选用三种代表不同CML急变期类型的细胞系（K562、EM-2和MOLM-1）及三位CML BC患者的原代白血病细胞，利用包含295种抗癌药物的敏感性及耐药性测试平台进行药物反应分析。总体而言，细胞系与原代细胞样本的药物敏感性评分及反应谱高度相关，且与其他白血病类型存在显著差异。细胞系对TKI类药物高度敏感，而临床表现为TKI耐药的患者样本在体外同样显示耐药性。通过对比细胞系与患者样本数据，我们发现了多种CML BC潜在治疗药物，如血管内皮生长因子受体抑制剂和烟酰胺磷酸核糖基转移酶抑制剂。研究结果表明，需通过扩大原代患者样本分析来重点评估这些药物的疗效。该成果还为设计合理的联合治疗方案奠定了基础。

原文链接：

Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing