成人急性淋巴细胞白血病（ALL）各亚型中威尔姆斯瘤基因1（WT1）的表达及其对临床结局的影响。

Wilms' tumor gene 1 (WT1) expression in subtypes of acute lymphoblastic leukemia (ALL) of adults and impact on clinical outcome.

作者信息

Busse Antonia, Gökbuget Nicola, Siehl Jan Michael, Hoelzer Dieter, Schwartz Stefan, Rietz Anika, Thiel Eckhard, Keilholz Ulrich

机构信息

Department of Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.

出版信息

Ann Hematol. 2009 Dec;88(12):1199-205. doi: 10.1007/s00277-009-0746-2. Epub 2009 Apr 29.

DOI:10.1007/s00277-009-0746-2

PMID:19404640

Abstract

Wilms' tumor gene 1 (WT1) is gaining increasing attention as a therapeutic target molecule due to its common expression in acute leukemias and its involvement in cell proliferation. Here, we reported on WT1 messenger RNA expression levels at diagnosis in a series of 238 adult acute lymphoblastic leukemia (ALL) samples of various subtypes and clinical outcome. WT1 expression was found in 219 out of 238 ALL samples (92%). Compared to a cohort of acute myeloid leukemia patients, the median WT1 expression level in ALL was significantly lower with large variations among different ALL subgroups. Specifically, WT1 expression levels were low in mature B-ALL and highest in ALL cases with co-expression of myeloid markers, making it a useful therapeutic target molecule in adult ALL with the exception of mature B-ALL. Cox regression analysis, considering ALL phenotype as well as molecular-cytogenetic subsets, revealed no independent prognostic role of WT1 expression level for disease-free and overall survival.

摘要

肾母细胞瘤基因1（WT1）因其在急性白血病中的普遍表达及其在细胞增殖中的作用，作为一种治疗靶点分子受到越来越多的关注。在此，我们报告了一系列238例不同亚型的成人急性淋巴细胞白血病（ALL）样本在诊断时的WT1信使核糖核酸表达水平及临床结局。在238例ALL样本中有219例（92%）检测到WT1表达。与急性髓系白血病患者队列相比，ALL中WT1表达水平的中位数显著更低，且在不同ALL亚组间存在较大差异。具体而言，成熟B-ALL中WT1表达水平较低，而在同时表达髓系标志物的ALL病例中最高，这使得WT1成为除成熟B-ALL外成人ALL中一个有用的治疗靶点分子。考虑到ALL表型以及分子细胞遗传学亚组的Cox回归分析显示，WT1表达水平对无病生存和总生存无独立预后作用。