title: EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages.
abstract: OBJECTIVE
  Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in myeloid leukemia. We therefore studied its expression and function in cluster of differentiation 34-positive (CD34(+)) primary human hematopoietic progenitor cells.
  
  
  METHODS
  CD34(+) cells were differentiated into various myeloid lineages using the appropriate cytokines. EVI1 expression was measured by quantitative real time reverse transcriptase-polymerase chain reaction (qRT-PCR) and intranuclear fluorescence-activated cell sorting (FACS). Experimental manipulation of EVI1 levels was achieved using retroviral infection.
  
  
  RESULTS
  EVI1 mRNA and its variant myelodysplastic syndrome 1 (MDS1)/EVI1, which gives rise to a partially antagonistic protein, were detectable in CD34(+) cells, but their levels declined rapidly during differentiation into the granulocyte, monocyte, dendritic, erythroid, and megakaryocyte lineages. Similarly, EVI1 protein levels decreased during myeloid differentiation. Attempts to experimentally express EVI1 in CD34(+) and U937 cells indicated that ectopic expression of EVI1 may cause growth arrest, apoptosis and/or senescence of human hematopoietic cells.
  
  
  CONCLUSIONS
  EVI1 is expressed in human hematopoietic progenitor cells, but is down-regulated during differentiation. Ectopic expression of EVI1 may activate cellular safeguards against oncogene activation.
authors.affiliation: Department of Medicine I, Medical University Vienna, Währinger Gürtel 18-20, 1090 Wien, Austria.
authors.forename: Katarina
authors.initials: K
authors.lastname: Steinleitner
authors.forename: Paulina
authors.initials: P
authors.lastname: Rampetsreiter
authors.forename: Rene
authors.initials: R
authors.lastname: Köffel
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Ramanathan
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
authors.forename: Herbert
authors.initials: H
authors.lastname: Strobl
authors.forename: Rotraud
authors.initials: R
authors.lastname: Wieser
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D011519:Proto-Oncogenes; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis*; D020298:U937 Cells
chemical_list: D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors