Leukemogenesis of the EVI1/MEL1 gene family.
Leukemia is a group of monoclonal diseases that arise from hematopoietic stem and progenitor cells in the bone marrow or other hematopoietic organs. Retroviral infections are one of the major events leading to leukemogenesis in mice, because retroviruses can induce hematopoietic disease via the insertional mutagenesis of oncogenes; therefore, the cloning of viral-integration sites in murine leukemia has provided valuable molecular tags for oncogene discovery. Transcription of the murine gene ecotropic viral-integration site 1 (Evi1) is activated by nearby viral integration. In humans, the Evi1 homologue EVI1 is activated by chromosomal translocations. This review discusses the roles of the overexpression of EVI1/MEL1 gene family members in leukemogenesis, the relationships of various translocations in EVI1 overexpression, and the importance of PR domains in tumor suppression and oncogenesis. The functions of EVI1/MEL1 members as transcription factors and the concept of EVI1-positive leukemia as a stem cell disease are also reviewed.
Morishita
Kazuhiro
K
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan. kmorishi@med.miyazaki-u.ac.jp
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; C416371:PRDM16 protein, human; D014157:Transcription Factors