文章：

外周血WT1-mRNA表达对MDS患者预后的影响

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS

原文发布日期：2019-11-12

DOI: 10.1038/s41408-019-0248-y

类型: Article

开放获取: 是

英文摘要：

Few reports suggested a prognostic impact of Wilms‘Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.
 

摘要翻译： 

少数报告提示Wilms肿瘤-1(WT1)mRNA过表达对骨髓增生异常综合征(MDS)具有预后影响，但受限于患者数量不足、样本来源差异及方法/截断值缺乏标准化，该指标未能转化为临床常规应用。为评估WT1-mRNA表达是否能提供额外预后信息，我们采用经验证可区分正常与过表达的标准化检测方法，检测了94例MDS患者的外周血WT1-mRNA表达水平。结果显示54例患者（57%）存在WT1-mRNA过表达，40例患者（43%）表达水平正常。该方法能有效区分MDS与健康对照组及非MDS血细胞减少症。进一步分析表明，WT1-mRNA表达水平与WHO 2016亚型分类及IPSS-R评分系统存在关联，具体体现在各亚组患者的平均WT1-mRNA表达量及过表达患者分布频率。整体队列中，单变量分析显示外周血WT1-mRNA过表达患者具有更高的疾病进展风险、急性髓系白血病转化风险，以及更短的无进展生存期、无白血病生存期和总生存期。多变量分析证实，外周血WT1-mRNA表达状态的预后价值独立于IPSS-R评分系统，且在IPSS-R极低危/低危和中危组中能更精准预测无进展生存期（但非总生存期）。综上，检测外周血WT1-mRNA表达有助于支持MDS诊断并优化IPSS-R评分系统的预后预测效能。

原文链接：

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS