Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells.
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.
Pubmed ID: 18682242 RIS Download
Animals | Bone Marrow Cells | Cell Line, Transformed | Cell Lineage | Cell Proliferation | Cell Survival | DNA-Binding Proteins | Gene Dosage | Hematopoiesis | Hematopoietic Stem Cell Transplantation | Hematopoietic Stem Cells | Humans | Leukemia, Myeloid | Mice | Mice, Inbred C57BL | Mice, Knockout | Microarray Analysis | Proto-Oncogenes | Receptor, TIE-2 | Transcription Factors