Shh信号通路在骨髓增生异常综合征和转白血病患者骨髓CD34^+细胞中的表达及临床意义

Expression and Significance of Shh Signaling Pathway in Bone Marrow CD34^+Cells of Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia with Myelodysplasia-Related Changes

目的:研究Shh信号通路相关基因Shh、Ptch1、Smo和Gli1在骨髓增生异常综合征(MDS)和MDS转白血病(AML-MRC)患者骨髓CD34^+细胞中的表达及其对预后的影响。方法:对53例MDS和30例AML-MRC患者采用流式细胞术检测骨髓CD34^+细胞数,磁珠分选CD34^+细胞,采用荧光实时定量PCR法检测CD34^+细胞上Shh、Ptch1、Smo和Gli1基因的表达,比较4种基因在MDS和AML-MRC患者中的表达及对预后的影响,并以25例缺铁性贫血患者作为对照。结果:Shh、Smo和Gli1在MDS组和AML-MRC组患者中的表达水平均显著高于对照组(P<0.05),且表达水平随疾病进展呈递增趋势(P<0.05);Ptch1表达在3组间差异无统计学意义(P>0.05)。与相对低危组比较,Smo和Gli1在相对高危组和AML-MRC组中的表达水平均明显增高(P<0.05)。MDS组和AMLMRC组患者中位生存时间分别为12(7.5,16.5)和6(3.0,9.0)个月(P=0.000)。生存分析显示,MDS和AMLMRC组中Smo和Gli1高表达患者的中位生存时间明显短于低表达患者(P<0.05)。结论:MDS肿瘤干细胞中存在Shh信号通路的活化,其参与了MDS疾病进展并影响患者预后。

Objective:To study the expression of Shh singaling related gene,including Shh,Ptch1,Smo and Gli1 in bone marrow CD34^+cells of patients with myelodysplastic syndrome(MDS)and acute myeloid leukemia with myelodysplasia-related changes(AML-MRC),and to explore their clinical significance.Methods:The count of CD34^+cells in bone marrow was detected by flow cytometry in 53 patients with MDS and 30 patients with AML-MRC.Magnetic beads were used to separate CD34^+cells.The expression of Shh,Ptch1,Smo and Gli1 on CD34^+cells was detected by qRT-PCR,the effect of the 4 gene expression on prognosis of patients in MDS and AML-MRC group was compared,25 patients with iron-deficiency anemia were used as controls.Results:The expression levels of Shh,Smo and Gli1 of patients in MDS and AML-MRC group were significantly higher than those in control group(P<0.05),moreover increased with disease progression(P<0.05).The expression of Ptch1 was not statistically significantly different between 3 groups(P>0.05).In comparison of prognosis,the expression of Smo and Gli1 in the patients of relatively high risk groups and AML-MRC groups were significantly increased(P<0.05).The median overall survival time of patients in MDS and AML-MRC groups was 12(7.5,16.5)and 6(3.0,9.0)months(P=0.000)respectively.The median survival time of MDS and AML-MRC patients with high expression of Smo and Gli1 was significantly shorter than that of MDS and AML-MRC patients with low expression of Smo and Gli1(P<0.05).Conclusion:Shh signaling pathway in the patients with MDS is activated,which is involved in the progress and prognosis of MDS.