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WT1在成人急性髓系白血病中的表达:评估其作为预后因素的存在情况、程度及时间变化

WT1 Expression in Adult Acute Myeloid Leukemia: Assessing its Presence, Magnitude and Temporal Changes as Prognostic Factors.

作者信息

Ujj Zsófia, Buglyó Gergely, Udvardy Miklós, Beyer Dániel, Vargha György, Biró Sándor, Rejtő László

机构信息

Institute of Internal Medicine, Division of Haematology, University of Debrecen, 98 Nagyerdei körút, Debrecen, 4028, Hungary.

Department of Human Genetics, University of Debrecen, 98 Nagyerdei körút, Debrecen, 4028, Hungary.

出版信息

Pathol Oncol Res. 2016 Jan;22(1):217-21. doi: 10.1007/s12253-015-0002-0. Epub 2015 Nov 4.

Abstract

Expression of the gene Wilms tumor 1 (WT1) has been suggested as a marker of minimal residual disease in acute myeloid leukemia (AML), but literature data are not without controversy. Our aim was to assess the presence, magnitude and temporal changes of WT1 expression as prognostic factors. 60 AML patients were followed until death or the end of the 6-year observation period. Blood samples were taken at diagnosis, post-induction, during remission and in case of a relapse. Using quantitative real-time PCR, we determined WT1 expression from each sample, normalized it against the endogenous control gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and classified samples as negative, moderately positive or highly positive. We divided the patients into groups based on detected WT1 expression values, illustrated overall and disease-free survival on Kaplan-Meier curves, and compared differences between each group by the logrank test. Disappearance of WT1-positivity during chemotherapy had a favorable effect on survival. Interestingly, no difference was seen between the survivals of WT1-positive subgroups that expressed moderate or high levels of WT1 mRNA. A 1-log decrease in WT1 expression without becoming negative did not affect prognosis, either. Our results suggest that defining a cut-off value for WT1-positivity, rather than just using logarithmic figures of changes in gene expression, might have prognostic use in post-induction AML patients. We encourage further, larger-scale studies.

摘要

Wilms肿瘤1(WT1)基因的表达已被认为是急性髓系白血病(AML)微小残留病的一个标志物,但文献数据并非没有争议。我们的目的是评估WT1表达的存在、程度和时间变化作为预后因素。对60例AML患者进行随访直至死亡或6年观察期结束。在诊断时、诱导后、缓解期以及复发时采集血样。使用定量实时PCR,我们从每个样本中测定WT1表达,以内源性对照基因甘油醛-3-磷酸脱氢酶(GAPDH)进行标准化,并将样本分类为阴性、中度阳性或高度阳性。我们根据检测到的WT1表达值将患者分组,在Kaplan-Meier曲线上描绘总生存期和无病生存期,并通过对数秩检验比较每组之间的差异。化疗期间WT1阳性的消失对生存有有利影响。有趣的是,WT1 mRNA表达水平为中度或高度的WT1阳性亚组的生存期之间没有差异。WT1表达下降1个对数但未变为阴性也不影响预后。我们的结果表明,确定WT1阳性的临界值,而不仅仅是使用基因表达变化的对数数值,可能对诱导后AML患者有预后价值。我们鼓励进一步开展更大规模的研究。

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