Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Clin Transl Oncol. 2017 Oct;19(10):1241-1246. doi: 10.1007/s12094-017-1661-y. Epub 2017 Apr 25.
Resistance to glucocorticoid (GC) is a significant clinical problem in some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC resistance are time consuming and have limited reproducibility; in this study, we sought to define a new method of evaluating GC sensitivity and resistance in vitro.
Based on the mechanisms of GC resistance, we hypothesized that the dual-luciferase report (DLR) assay could reflect the transcription effects of GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby allowing the evaluation of reactions to GC. Sixty-two patients with differential GC response were included in this study. The prednisone induction test was used to divide the children with ALL into two groups: GC sensitive (GCS) and GC resistant (GCR). DLR assay was later conducted on those patients to evaluate its value for diagnosis of the GC reactivity. Receiver operating characteristic curves were used to identify the optimal assay cutoff for identifying response to GC.
Using the DLR assay analysis, we found that GCR subjects showed significantly lower reporter/control ratios for luciferase, as compared with GCS subjects. The optimal cutoff value for GC response was 0.67, with sensitivity of 77.1% and specificity of 93.3%. The DLR assay results were consistent with prednisone induction test results. Further, the DLR assay was simpler, more sensitive, and less time-consuming than the prednisone induction test.
Our study showed that the DLR assay is relatively fast, simple, and sensitive. Accordingly, it could be useful for detecting GC response in children with ALL.
在某些急性淋巴细胞白血病（ALL）病例中，对糖皮质激素（GC）的耐药性是一个重大的临床问题。目前评估 GC 耐药性的方法既耗时又重复性有限；在这项研究中，我们试图定义一种新的体外评估 GC 敏感性和耐药性的方法。
基于 GC 耐药的机制，我们假设双荧光素酶报告（DLR）测定可以反映 GC 下游 GC-糖皮质激素受体信号通路的转录效应，从而可以评估对 GC 的反应。本研究纳入了 62 例 GC 反应不同的患者。泼尼松诱导试验用于将 ALL 患儿分为 GC 敏感（GCS）和 GC 耐药（GCR）两组。随后对这些患者进行 DLR 测定，以评估其对 GC 反应性诊断的价值。受试者工作特征曲线用于确定识别 GC 反应的最佳测定截止值。
通过 DLR 测定分析，我们发现与 GCS 组相比，GCR 组的荧光素酶报告/对照比值明显较低。GC 反应的最佳截断值为 0.67，其敏感性为 77.1%，特异性为 93.3%。DLR 测定结果与泼尼松诱导试验结果一致。此外，DLR 测定比泼尼松诱导试验更简单、更敏感、耗时更短。
我们的研究表明，DLR 测定相对快速、简单且敏感。因此，它可能有助于检测 ALL 患儿的 GC 反应。
