骨髓增生异常综合征患者骨髓及外周血中WT1及PRAME基因的表达研究

Expression of WT1 and PRAME Gene in Bone Marrow and Peripheral Blood Samples of Patients with Myelodysplastic Syndrome

本研究探讨WT1及PRAME基因在骨髓增生异常综合征患者骨髓和外周血中的表达情况以及与核型异常、病态造血、血红蛋白值之间的关系。收集2009年7月至2012年6月在我院初诊的240例贫血患者,其中MDS203例(RCUD 15例,RCMD 25例,RAEB1 61例,RAEB2 55例,MDS-U 23例,MDS-AML 24例),AA 18例,其他良性贫血15例,PNH 4例和14例健康供者的骨髓标本,并收集其中78例患者及14例健康供者的外周血,分别检测骨髓和外周血中WT1及PRAME基因的表达水平。结果表明,WT1及PRAME在MDS骨髓及外周血中的表达均高于正常组、AA组及良性贫血组(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),其中高危MDS患者WT1及PRAME的表达均高于低危组,AA及其他良性贫血组,且WT1及PRAME在骨髓和外周血中的表达水平呈现良好的相关性(WT1:r=0.6028,P=0.001;PRAME:r=0.7628,P=0.000),WT1或PRAME在骨髓与外周血中阳性率一致(P=0.167);另外,骨髓中WT1的表达水平与核型异常相关(P=0.049)。结论:MDS患者骨髓及外周血WT1和PRAME的表达较正常人、AA及其他良性贫血患者升高,且随着病情进展,其表达增加;WT1和PRAME基因的表达上调是MDS很好的分子标记,联合运用WT1和PRAME基因表达水平检测能为MDS的临床诊断及预后判断和微小残留监测提供有用信息,且在骨髓取材不便的时候可用外周血代替监测。

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 dys- plasia and karyotype. The quantitative expression of WT1 and PRAME transcripts detected by RQ-PCR in the bone mar- row samples of 203 MDS patients and 19 aplastic anemia（ AA）, 6 other benign anemia（ BA）, 4 paroxysmai nocturnal hemoglobinu- ria（PNH） patients from July 2009 to June 2012 and 14 healthy donors, and in 92 peripheral blood sam- ples. 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 pa- tients. 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 dis- ease. 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 toget, the transcript levels of PB samples can be detected.