1. Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7
2. Department of Medicine, Hospital Maisonneuve-Rosemont, Montreal, Montreal University, Montreal, Quebec, Canada, H3C 3J7
3. Division of Hematology, Hospital Maisonneuve-Rosemont, Montreal, Montreal University, Montreal, Quebec, Canada, H3C 3J7

Correspondence to: Guy Sauvageau^1,2,3 Correspondence and requests for materials should be addressed to G.S. (Email: sauvagg@ircm.qc.ca).

Abstract

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.