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Nature. 2003 May 15;423(6937):255-60. Epub 2003 Apr 20.

Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.

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Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7.


An emerging concept in the field of cancer biology is that a rare population of 'tumour stem cells' exists among the heterogeneous group of cells that constitute a tumour. This concept, best described with human leukaemia, indicates that stem cell function (whether normal or neoplastic) might be defined by a common set of critical genes. Here we show that the Polycomb group gene Bmi-1 has a key role in regulating the proliferative activity of normal stem and progenitor cells. Most importantly, we provide evidence that the proliferative potential of leukaemic stem and progenitor cells lacking Bmi-1 is compromised because they eventually undergo proliferation arrest and show signs of differentiation and apoptosis, leading to transplant failure of the leukaemia. Complementation studies showed that Bmi-1 completely rescues these proliferative defects. These studies therefore indicate that Bmi-1 has an essential role in regulating the proliferative activity of both normal and leukaemic stem cells.

[Indexed for MEDLINE]

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