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[WT1和PRAME基因在骨髓增生异常综合征患者骨髓及外周血样本中的表达]

[Expression of WT1 and PRAME gene in bone marrow and peripheral blood samples of patients with myelodysplastic syndrome].

作者信息

Lu Dan, Qin Ya-Zhen, Li Ling-Di, Shi Hong-Xia, Lai Yue-Yun, Liu Yan-Rong

机构信息

Institute of Hematology, Peking University People Hospital, Beijing 100044, China.

Institute of Hematology, Peking University People Hospital, Beijing 100044, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Apr;22(2):370-6. doi: 10.7534/j.issn.1009-2137.2014.02.019.

Abstract

This study was aimed to explore the transcription level of WT1 and PRAME two genes in bone marrow and peripheral blood samples of patients with myelodysplastic syndrome(MDS) and their relationship with bone marrow dysplasia and karyotype. The quantitative expression of WT1 and PRAME transcripts detected by RQ-PCR in the bone marrow samples of 203 MDS patients and 19 aplastic anemia(AA), 6 other benign anemia(BA), 4 paroxysmal nocturnal hemoglobinuria(PNH) patients from July 2009 to June 2012 and 14 healthy donors, and in 92 peripheral blood samples. The results showed that WT1 and PRAME expression levels in both BM and PB samples of MDS group were higher than those in normal controls, AA, and BA patients (BM: WT1:P = 0.000, 0.000, 0.000, PRAME: P = 0.048, 0.000, 0.064; PB: WT1:P = 0.012, 0.000, 0.011, PRAME: P = 0.020, 0.004, 0.003). What is more, this expression in high risk MDS group (RAEB1, RAEB2, MDS-AML) were higher than those in low risk group (RCUD, RCMD, MDS-U) and AA and BA. The WT1 and PRAME mRNA expression levels in PB and BM were well correlated (WT1:r = 0.6028, P = 0.001; PRAME: r = 0.7628, P = 0.000), as well as the WT1 expression levels in BM samples with the Karyotype (P = 0.049). In addition, the same positive rate of WT1 or PRAME expression existed in BM and PB samples of MDS patients. It is concluded that the WT1 and PRAME gene expression levels in both BM and PB samples of MDS patients are higher than those in healthy controls, AA and other benign anemia patients, and increase with the progression of the disease. The WT1 and PRAME transcripts constitute good molecular markers for the clinical diagnosis and prognosis and monitoring minimal residual disease after treatment of MDS. What is more, when bone marrow is not so convenient to get, the transcript levels of PB samples can be detected.

摘要

本研究旨在探讨骨髓增生异常综合征(MDS)患者骨髓和外周血样本中WT1和PRAME两个基因的转录水平及其与骨髓发育异常和核型的关系。通过RQ-PCR检测了2009年7月至2012年6月期间203例MDS患者、19例再生障碍性贫血(AA)患者、6例其他良性贫血(BA)患者、4例阵发性睡眠性血红蛋白尿(PNH)患者以及14例健康供者骨髓样本中WT1和PRAME转录本的定量表达,并检测了92例外周血样本。结果显示,MDS组骨髓和外周血样本中WT1和PRAME的表达水平均高于正常对照、AA和BA患者(骨髓:WT1:P = 0.000,0.000,0.000,PRAME:P = 0.048,0.000,0.064;外周血:WT1:P = 0.012,0.000,0.011,PRAME:P = 0.020,0.004,0.003)。此外,高危MDS组(RAEB1、RAEB2、MDS-AML)的这种表达高于低危组(RCUD、RCMD、MDS-U)以及AA和BA患者。外周血和骨髓中WT1和PRAME mRNA表达水平具有良好的相关性(WT1:r = 0.6028,P = 0.001;PRAME:r = 0.7628,P = 0.000),骨髓样本中WT1表达水平与核型也具有相关性(P = 0.049)。此外,MDS患者骨髓和外周血样本中WT1或PRAME表达的阳性率相同。结论是,MDS患者骨髓和外周血样本中WT1和PRAME基因表达水平高于健康对照、AA和其他良性贫血患者,并随疾病进展而升高。WT1和PRAME转录本构成了MDS临床诊断、预后评估及治疗后微小残留病监测的良好分子标志物。此外,当获取骨髓不方便时,可以检测外周血样本的转录水平。

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