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Cell Stem Cell. 2008 Aug 7;3(2):207-20. doi: 10.1016/j.stem.2008.06.002.

Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells.

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1
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

Abstract

Evi-1 has been recognized as one of the dominant oncogenes associated with murine and human myeloid leukemia. Here, we show that hematopoietic stem cells (HSCs) in Evi-1-deficient embryos are severely reduced in number with defective proliferative and repopulating capacity. Selective ablation of Evi-1 in Tie2(+) cells mimics Evi-1 deficiency, suggesting that Evi-1 function is required in Tie2(+) hematopoietic stem/progenitors. Conditional deletion of Evi-1 in the adult hematopoietic system revealed that Evi-1-deficient bone marrow HSCs cannot maintain hematopoiesis and lose their repopulating ability. In contrast, Evi-1 is dispensable for blood cell lineage commitment. Evi-1(+/-) mice exhibit the intermediate phenotype for HSC activity, suggesting a gene dosage requirement for Evi-1. We further demonstrate that disruption of Evi-1 in transformed leukemic cells leads to significant loss of their proliferative activity both in vitro and in vivo. Thus, Evi-1 is a common and critical regulator essential for proliferation of embryonic/adult HSCs and transformed leukemic cells.

PMID:
18682242
DOI:
10.1016/j.stem.2008.06.002
[Indexed for MEDLINE]
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