Zhong Ling, Wei Lingling, Chen Jiao, Huang Xiaobing, Gong Yuping, Lu Yanrong
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Gaopeng Avenue, Chengdu, 610041, People's Republic of China.
Mol Diagn Ther. 2015 Aug;19(4):205-12. doi: 10.1007/s40291-015-0147-2.
Circulating RNA in plasma (CRNA) refers to soluble tumor-derived ribonucleic acids (RNA). The Wilms tumor 1 (WT1) gene appears to be a highly promising marker for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients after chemotherapy or hematopoietic stem-cell transplantation (HSCT).
This study aimed to compare the relative expression level of the WT1 gene in CRNA, bone marrow (BM)- and peripheral blood (PB)-RNA for the monitoring of MRD in AML patients after HSCT.
One hundred and eighteen AML patients were studied with WT1 expression assessed by quantitative polymerase chain reaction in plasma, BM- and PB-RNA. Correlation analysis was used to compare gene expression differences.
The expression of the WT1 gene was successfully detected in 118 cases but was absent in controls (mean relative expression of WT1/ABL 8.77, range 0.5-56.0, P < 0.001) (WT1 in BM-RNA: mean relative expression 8.66, range 0.5-56.0, P < 0.001; WT1 in PB-RNA: mean relative expression 8.55, range 0.5-54.0, P < 0.001). WT1 expression in CRNA, BM-RNA and PB-RNA showed no difference at diagnosis (CRNA vs. BM-RNA, r = 0.999; CRNA vs. PB-RNA, r = 0.988). After HSCT, 62 patients achieved remission. The expression level of WT1 in CRNA and BM-RNA in nine patients who achieved permanent remission fluctuated within the normal range (WT1/ABL < 0.02). The other 53 patients who were predicted to relapse had elevated WT1 levels in CRNA and BM-RNA. Of these 53 patients, 48 had increased expression of the WT1 gene in both CRNA and BM-RNA at a median of 1 month prior to clinical relapse. In the other five patients (5/53) diagnosed with extramedullary relapse, the level of WT1 in CRNA was elevated prior to relapse. However, in these patients WT1 expression in both BM-RNA and PB-RNA was still negative (at a median of 1 month earlier than in BM-RNA). This study indicated that CRNA was no different from BM-RNA for determination of WT1 expression in AML patients (F = 0.260, P = 0.642).
Analysis of WT1 expression in CRNA in AML patients could be a simple, convenient and noninvasive method to predict latent information about relapse.
血浆中的循环RNA（CRNA）是指可溶性肿瘤来源的核糖核酸（RNA）。威尔姆斯瘤1（WT1）基因似乎是急性髓系白血病（AML）患者化疗或造血干细胞移植（HSCT）后微小残留病（MRD）检测中一个非常有前景的标志物。
本研究旨在比较CRNA、骨髓（BM）和外周血（PB）RNA中WT1基因的相对表达水平，以监测HSCT后AML患者的MRD。
对118例AML患者进行研究，通过定量聚合酶链反应评估血浆、BM和PB RNA中的WT1表达。采用相关性分析比较基因表达差异。
在118例患者中成功检测到WT1基因表达，但在对照组中未检测到（WT1/ABL的平均相对表达为8.77，范围为0.5 - 56.0，P < 0.001）（BM RNA中的WT1：平均相对表达为8.66，范围为0.5 - 56.0，P < 0.001；PB RNA中的WT1：平均相对表达为8.55，范围为0.5 - 54.0，P < 0.001）。CRNA、BM RNA和PB RNA中WT1的表达在诊断时无差异（CRNA与BM RNA比较，r = 0.999；CRNA与PB RNA比较，r = 0.988）。HSCT后，62例患者达到缓解。9例获得永久缓解的患者中，CRNA和BM RNA中WT1的表达水平在正常范围内波动（WT1/ABL < 0.02）。其他53例预计复发的患者中，CRNA和BM RNA中WT1水平升高。在这53例患者中，48例在临床复发前1个月时CRNA和BM RNA中WT1基因表达均增加。在另外5例（5/53）诊断为髓外复发的患者中，CRNA中WT1水平在复发前升高。然而，这些患者BM RNA和PB RNA中的WT1表达仍为阴性（比BM RNA早1个月）。本研究表明AML患者中CRNA与BM RNA在WT1表达测定方面无差异（F = 0.260，P = 0.642）。
分析AML患者CRNA中WT1的表达可能是一种简单、方便且无创的方法，用于预测复发的潜在信息。
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