title: Paroxysmal nocturnal hemoglobinuria: Differential gene expression of EGR-1 and TAXREB107.
abstract: OBJECTIVE
  Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect of hematopoietic stem cells characterized by deficiency in GPI-anchored surface proteins. It is not yet known how GPI-deficient stem cells are able to expand within the bone marrow and contribute considerably to the hematopoiesis. In PNH, as well as in AA and MDS, genetic instability and increased mutation frequency have been detected. Therefore, a second event is very likely, such as additional mutations, leading to clonal expansion of GPI-deficient bone marrow stem cell in PNH.
  
  
  METHODS
  In order to elucidate the molecular basis of clonal expansion in PNH, we identified several genes differentially expressed in normal and GPI-deficient cells of PNH patients by combination of RNA fingerprinting and cDNA array hybridization.
  
  
  RESULTS
  Expression of two of these genes, EGR-1 and TAXREB107, has been further investigated. EGR-1 is upregulated in granulocytes of all PNH patients analyzed so far. In contrast, significant upregulation of TAXREB107 is present only in some of our PNH patients. Further analysis confirmed their overexpression in PNH and excluded a possible secondary event character of observed overexpression. Moreover, similar levels of expression in cases of other clonal diseases, such as MPS and MDS, has been identified.
  
  
  CONCLUSIONS
  Our data suggest that additional genetic alterations apart from PIG-A mutations could be present in PNH granulocytes. In addition, these genetic changes might contribute to clonal expansion of GPI-deficient cells in PNH.
authors.affiliation: Dept. of Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Lyakisheva
authors.forename: Olga
authors.initials: O
authors.lastname: Felda
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Jörg
authors.initials: J
authors.lastname: Schubert
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D016356:Gene Products, tax; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins; D008875:Middle Aged; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016356:Gene Products, tax; D017874:Immediate-Early Proteins; D014157:Transcription Factors; C093544:tax-responsive-element-binding protein 107, mouse