Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
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.
Lessard
Julie
J
Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada, H2W 1R7.
Sauvageau
Guy
G
D000818:Animals; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
C489421:Bmi1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1