Real-time fluorescent resonance energy transfer analysis to monitor drug resistance in chronic myelogenous leukemia.
Real-time fluorescent resonance energy transfer analysis to monitor drug resistance in chronic myelogenous leukemia.
复制标题
实时荧光共振能量转移分析监测慢性粒细胞白血病的耐药性。
DOI：
10.1158/1535-7163.mct-10-0623
复制
发表时间：
2010
影响因子：
5.7
通讯作者：
Birge,RaymondB
中科院分区：
文献类型：
--
作者：
Tunceroglu,Ahmet;Matsuda,Michiyuki;Birge,RaymondB
Despite the initial effectiveness of oncogene-directed cancer therapeutics, acquired drug resistance remains the ultimate “Achilles' heel” for long-term durable remission in cancer patients. Acquisition of drug resistance is not more evident elsewhere than in the use of tyrosine kinase inhibitors, imatinib and dasatinib, for patients with chronic myelogenous leukemia. Hence, even though imatinib initially produces remission in the chronic phase, ultimately these therapeutics fail via the emergence of drug resistance, in which chronic myelogenous leukemia could inevitably progress to a terminal blast phase culminating in fatal outcome. Technically, it is challenging to predict the onset of drug resistance in a small number of oncogene-transformed cells, making the decision of when and how to employ second-generation tyrosine kinase inhibitors, or employ novel compounds that would be of benefit in treating drug-resistant Bcr-Abl mutants mainly retrospective. Here, we characterize a rapid and sensitive real-time fluorescent resonance energy transfer–based assay that is able to detect thein vivoactivity of Bcr-Abl and its inhibition by small molecule compounds. Due to its real-time andin vivonature, such an approach has the potential to monitor a drug-resistant phenotype, as well as to identify pharmaceutical agents that inhibit drug-resistant Bcr-Abl oncoproteinsin vivo. Mol Cancer Ther; 9(11); 3065–73. ©2010 AACR.
