Using the geometric mean fluorescence intensity index method to measure ZAP-70 expression in patients with chronic lymphocytic leukemia.
Using the geometric mean fluorescence intensity index method to measure ZAP-70 expression in patients with chronic lymphocytic leukemia.
复制标题
几何平均荧光强度指数法测定慢性淋巴细胞白血病患者ZAP-70的表达
DOI：
10.2147/ott.s94613
复制
发表时间：
2016
影响因子：
4
通讯作者：
Li JY
中科院分区：
文献类型：
--
作者：
Wu YJ;Wang H;Liang JH;Miao Y;Liu L;Qiu HR;Qiao C;Wang R;Li JY
ζ链相关蛋白激酶70 kDa在慢性淋巴细胞白血病中的表达与疾病的侵袭性有关，有助于与表达突变或非突变免疫球蛋白重链可变区基因的患者区分开来。然而，通过流式细胞仪分析来标准化ZAP-70的表达已被证明是不令人满意的。关键是ZAP-70的弱表达呈连续表达模式，而不是对阳性和阴性的CLL细胞进行明显的区分，这意味着由此产生的判断是主观的。因此，在本研究中，我们旨在使用基于256通道分辨率的流式细胞术的几何平均荧光强度(Geo MFI)指数法来评估ZAP-70在402例CLL患者中表达的可靠性和重复性，并将ZAP-70与其他生物学和临床预测指标进行比较。根据IgHV变异情况，我们能够确定在测试集中Geo MFI指数的最佳截断点为3.5。在包括CLL的主要临床和生物学预后指标的多因素分析中，当应用Geo MFI指数方法时，ZAP-70的表达对预后的影响似乎具有更强的区分性。此外，根据Geo MFI指数法，ZAP-70阳性患者首次治疗时间或总生存期较短(P=0.0002，P=0.0491)。这是第一个表明ZAP-70的表达可以通过一种新的方法--Geo MFI指数来评估的报道，这可能是一种有用的预后方法，因为它更可靠，主观性更小，因此与改善CLL预后和预测临床病程有更好的相关性。
Expression of ζ-chain-associated protein kinase 70 kDa (ZAP-70) in chronic lymphocytic leukemia (CLL) is associated with more aggressive disease and can help differentiate CLL from cases expressing mutated or unmutated immunoglobulin heavy chain variable region (IgHV) genes. However, standardizing ZAP-70 expression by flow cytometric analysis has proved unsatisfactory. The key point is that ZAP-70 is weakly expressed with a continuous expression pattern rather than a clear discrimination between positive and negative CLL cells, which means that the resulting judgment is subjective. Thus, in this study, we aimed at assessing the reliability and repeatability of ZAP-70 expression using the geometric mean fluorescence intensity (geo MFI) index method based on flow cytometry with 256-channel resolution in a series of 402 CLL patients and to compare ZAP-70 with other biological and clinical prognosticators. According to IgHV mutational status, we were able to confirm that the optimal cut-off point for the geo MFI index was 3.5 in the test set. In multivariate analyses that included the major clinical and biological prognostic markers for CLL, the prognostic impact of ZAP-70 expression appeared to have stronger discriminatory power when the geo MFI index method was applied. In addition, we found that ZAP-70-positive patients according to the geo MFI index method had shorter time to first treatment or overall survival (P=0.0002,P=0.0491). This is the first report showing that ZAP-70 expression can be evaluated by a new approach, the geo MFI index, which could be a useful prognostic method as it is more reliable, less subjective, and therefore better associated with improvement of CLL prognostication and prediction of clinical course.