title: [Significance of interplay between Rap1 and cadherin to the development of myelodysplastic syndrome].
abstract: OBJECTIVE
  To explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/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 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Affiliated Children's Hospital, Soochow University, Suzhou 215003, China.
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Shao
authors.forename: Mei-hua
authors.initials: MH
authors.lastname: Miao
authors.forename: Zi-xing
authors.initials: ZX
authors.lastname: Chen
authors.forename: Xiao-fei
authors.initials: XF
authors.lastname: Qi
authors.forename: Hong-jie
authors.initials: HJ
authors.lastname: Shen
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics; D020827:rap1 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin; D020827:rap1 GTP-Binding Proteins