The role of EVI1 in myeloid malignancies.
The EVI1 oncogene at human chr 3q26 is rearranged and/or overexpressed in a subset of acute myeloid leukemias and myelodysplasias. The EVI1 protein is a 135 kDa transcriptional regulator with DNA-binding zinc finger domains. Here we provide a critical review of the current state of research into the molecular mechanisms by which this gene plays a role in myeloid malignancies. The major pertinent cellular effects are blocking myeloid differentiation and preventing cellular apoptosis, and several potential mechanisms for these phenomena have been identified. Evidence supports a role for EVI1 in inducing cellular quiescence, and this may contribute to the resistance to chemotherapy seen in patients with neoplasms that overexpress EVI1. Another isoform, MDS1-EVI1 (or PRDM3), encoded by the same locus as EVI1, harbors an N-terminal histone methyltransferase(HMT) domain; experimental findings indicate that this protein and its HMT activity are critical for the progression of a subset of AMLs, and this provides a potential target for therapeutic intervention.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Carolyn
C
Glass
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Michael
M
Wilson
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Ruby
R
Gonzalez
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Yi
Y
Zhang
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address: archibald_perkins@urmc.rochester.edu.
Archibald S
AS
Perkins
D000818:Animals; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic; D056426:Genetic Loci; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D011519:Proto-Oncogenes / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors
Apoptosis; Differentiation; EVI1; Leukemogenesis; Myeloid leukemia; Oncogenes