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Rapl及cadherin基因表达异常在骨髓增生异常综合征发病中的意义 被引量:3

Significance of interplay between Rapl and cadherin to the development of myelodysplastic syndrome
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摘要 目的通过分析骨髓增生异常综合征(MDS)患者骨髓造血干/祖细胞造血调控相关基因表达谱,探讨MDS发生的病理生理机制。方法先采用全基因组表达谱芯片筛选MDS患者CD34+细胞造血调控相关差异表达基因,再用实时荧光定量PCR(RQ—PCR)法验证这些差异表达基因在核型正常的MDS-难治性贫血(RA)患者CD34+细胞中是否也存在差异表达,分析差异表达基因与造血调控的内在联系。结果MDS—RA患者CD34+细胞RaplGAP基因表达显著上调(P〈0.01),而与Rapl存在反馈调节作用的黏附分子cadherin,包括N—cadhefin和E.cadhefin的表达显著下调(P值均〈0.01),其下游靶分子B—catenin的表达显著增高(P〈0.01)。c—myc结合蛋白基因表达显著下调(P〈0.01),c—myc启动子结合蛋白基因表达显著上调(P〈0.01)。既参与造血,又与细胞形态密切相关的RhoGTPases家族分子Racl、Rac2和Cdc42的表达水平显著上调(P值均〈0.01)。结论Cadherin、β-catenin和c—myc相关基因表达异常与MDS的病态造血密切相关,cadherin的下调与Rapl的正反馈调节相关,Racl、Rac2和Cdc42基因表达异常可能与MDS骨髓细胞形态异常相关。 Objective To explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stern/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis. Methods The differentially expressed genes which were involved in the hematopoiesis were screened by mi- croarray 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. Results Among the differentially expressed genes in CD34 ~ cells of MDS-RA patients, Rapl GAP was up-regulated significantly (P 〈 0.01 ). Cadherins, which can inter- play with Rapl, including N-cadherin and E-cadherin, were down-regulated significantly ( P 〈 0.01 ). [5- catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients ( P 〈 0.01 ). e-myc binding protein was down-regulated( P 〈 0.01 ) , and c-myc promoter binding protein was up-regulated ( P 〈 0.01 ). Racl, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell mor- phology and hematopoiesis, were all expressed highly in MDS-RA patients ( P 〈 0.01 ). Conclusion The ab- normal expression of eadherin, [3-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 Rapl and cadherin. The aberrant expression of Racl, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2012年第7期522-526,共5页 Chinese Journal of Hematology
基金 国家自然科学基金(81070402) 江苏省高校优势学科建设工程项目(PAPD)
关键词 骨髓增生异常综合征 基因 Rapl 基因 cadherin 造血干细胞 Myelodysplastic syndrome Gene, Rapl Gene, cadherin Hematopoietic stem cells
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共引文献2

同被引文献35

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