Shao Xue-jun, Miao Mei-hua, Chen Zi-xing, Qi Xiao-fei, Shen Hong-jie
The Affiliated Children's Hospital, Soochow University, Suzhou 215003, China.
Zhonghua Xue Ye Xue Za Zhi. 2012 Jul;33(7):522-6.
To explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis.
The differentially expressed genes which were involved in the hematopoiesis were screened by microarray using CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype. The linkages with hematopoiesis among these validated genes were analyzed.
Among the differentially expressed genes in CD34(+) cells of MDS-RA patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated significantly (P < 0.01). β-catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down-regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P < 0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA patients (P < 0.01).
The abnormal expression of cadherin, β-catenin and c-myc associated genes were closely related to the dysplastic hematopoiesis of MDS. The down regulation of cadherin was associated with the positive feedback mechanism between Rap1 and cadherin. The aberrant expression of Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.
通过分析与造血相关的基因表达谱，在干/祖细胞水平探讨骨髓增生异常综合征（MDS）的造血病理生理学。
首先使用MDS患者的CD34(+)细胞通过微阵列筛选参与造血的差异表达基因。然后应用实时定量聚合酶链反应（RQ-PCR），使用核型正常的MDS-RA患者的CD34(+)细胞验证筛选出的基因。分析这些验证基因之间与造血的联系。
在MDS-RA患者的CD34(+)细胞中差异表达的基因中，Rap1GAP显著上调（P < 0.01）。可与Rap1相互作用的钙黏蛋白，包括N-钙黏蛋白和E-钙黏蛋白，显著下调（P < 0.01）。作为钙黏蛋白下游效应物的β-连环蛋白在MDS-RA患者中高表达（P < 0.01）。c-myc结合蛋白下调（P < 0.01），而c-myc启动子结合蛋白上调（P < 0.01）。属于RhoGTPases家族且与细胞形态和造血相关的Rac1、Rac2和Cdc42在MDS-RA患者中均高表达（P < 0.01）。
钙黏蛋白、β-连环蛋白和c-myc相关基因的异常表达与MDS的造血异常密切相关。钙黏蛋白的下调与Rap1和钙黏蛋白之间的正反馈机制有关。Rac1、Rac2和Cdc42的异常表达可能导致MDS的形态异常。
