• Open Access

Ecotropic viral integration site 1, stem cell self-renewal and leukemogenesis



It has become evident that acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells. Recent gene expression profile analysis of human leukemia stem cells and hematopoietic stem cell (HSC) populations identified a key transcriptional program shared by leukemia stem cells and HSC, which is associated with adverse outcomes in AML patients. One molecule that has been established as a pivotal regulator in fine-tuning of stem cell properties as well as a potent oncogenic determinant is ecotropic viral integration site 1 (EVI1). EVI1 is a transcription factor that has stem cell-specific expression pattern and is essential for the regulation of HSC self-renewal. This gene is notorious for its involvement in AML, as its activation confers extremely poor prognosis in patients with AML. Molecular analysis has identified a variety of gene products that are involved in HSC regulation as downstream targets or interacting proteins of EVI1. Thus, exploration of the molecular pathogenesis underlying EVI1-related leukemogenesis provides insight into how shared stemness transcriptional programs contribute to leukemia progression and therapeutic resistance in AML. Here, we review the current knowledge regarding the role of EVI1 in HSC self-renewal and leukemogenesis and highlight the relationship between stem cell self-renewal properties and adverse outcome in myeloid malignancies. (Cancer Sci, doi: 10.1111/j.1349-7006.2012.02303.x, 2012)