Koczkodaj Dorota, Zmorzyński Szymon, Grygalewicz Beata, Pieńkowska-Grela Barbara, Styk Wojciech, Popek-Marciniec Sylwia, Filip Agata Anna
Department of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, 20-059 Lublin, Poland.
The Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland.
J Clin Med. 2022 Mar 28;11(7):1873. doi: 10.3390/jcm11071873.
(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes—10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p < 0.0001) and affected relapse-free survival (RFS). The presence of NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02−0.46, p = 0.002 or OR = 0.05, 95% CI 0.006−0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.
(1) 背景：我们研究的目的是对急性髓系白血病（AML）中WT1基因变异及其表达与染色体变化和分子预后标志物的关系进行综合评估。这是波兰AML患者的首个多维度研究；(2) 方法：90例AML患者的骨髓穿刺液用于细胞培养（显带技术和荧光原位杂交）、DNA分离（WT1基因分型、阵列比较基因组杂交）以及RNA提取（WT1表达分析）。100名健康献血者的外周血样本用于分析WT1 rs16754；(3) 结果：AML患者和对照组之间WT1变异rs16754（A；G）的等位基因频率和分布无显著差异。与GA或GG基因型相比，AA基因型（rs16754）中WT1基因表达更高，分别为10,556.7拷贝对25,836.5拷贝（p = 0.01）。WT1突变在65岁以下的AML患者中更常见（p < 0.0001），并影响无复发生存期（RFS）。NPM1或CEBPA突变的存在降低了WT1突变出现的风险，优势比（OR）分别为0.11，95%置信区间0.02 - 0.46，p = 0.002或OR = 0.05，95%置信区间0.006 - 0.46，p = 0.002。我们观察到AML中CD34 +细胞与CD34 -细胞相比，WT1表达显著更高，分别为 - 20,985对8304（p = 0.039）。核型正常与异常的患者之间WT1表达差异无统计学意义；(4) 结论：诊断时WT1基因表达及其rs16754变异不影响AML的预后。WT1突变可能影响AML的RFS。
