title: Pathogenetic significance of ecotropic viral integration site-1 in hematological malignancies.
abstract: The ecotropic viral integration site-1 (Evi-1) gene was first identified as a common locus of retroviral integration in murine leukemia models. In humans, EVI-1 is located on chromosome 3q26, and rearrangements on chromosome 3q26 often activate EVI-1 expression in hematological malignancies. Overexpression of EVI-1 also occurs with high frequency in leukemia patients without 3q26 abnormalities, and importantly, high EVI-1 expression is an independent negative prognostic indicator irrespective of the presence of 3q26 rearrangements. Recent gene targeting studies in mice revealed that Evi-1 is preferentially expressed in hematopoietic stem cells and plays an essential role in proliferation and maintenance of hematopoietic stem cells. In addition, intense attention has been focused on the EVI-1 gene complex as retrovirus integration sites because transcription-activating integrations into the EVI-1 locus confer survival and self-renewing ability to hematopoietic cells. The experimental results using animal models suggest that activation of Evi-1 in hematopoietic cells leads to clonal expansion or dysplastic hematopoiesis, whereas onset of full-blown leukemia requires cooperative genetic events. EVI-1 possesses diverse functions as an oncoprotein, including suppression of transforming growth factor-beta-mediated growth inhibition, upregulation of GATA2, inhibition of the Jun kinase pathway, and stimulation of cell growth via activator protein-1. In this article, we summarize current knowledge regarding the biochemical properties and biological functions of EVI-1 in normal and malignant hematopoiesis, with specific focus on its pathogenetic significance in hematological malignancies.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Goyama
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D014644:Genetic Variation; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000821:virology*; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000235:genetics; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D016662:Virus Integration / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D012333:RNA, Messenger; D014157:Transcription Factors