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

Nature. 2003 May 15;423(6937):255-60. doi: 10.1038/nature01572. Epub 2003 Apr 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • Gene Deletion
  • Genotype
  • Leukemia / metabolism
  • Leukemia / pathology*
  • Liver / cytology
  • Liver / embryology
  • Liver / metabolism
  • Mice
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins*
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • Bmi1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1