Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
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.
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Knockout of p16 increases the life-span of HSCs by promoting HSC self-renewal.
“but knockout of p16 increases the life-span of HSCs by promoting HSC self-renewal.16-19”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [16]
Knockout of both the p16 and Arf genes in mice significantly increases the clonal expansion of HSCs in vitro but modestly promotes HSC self-renewal in vivo.
“In addition, it has been found that knockout of both the p16 and Arf genes in mice significantly increases the clonal expansion of HSCs in vitro but modestly promotes HSC self-renewal in vivo.16”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [16]
Knockout of the Arf gene alone provides no significant advantage for HSC/HPC expansion and self-renewal.
“Knockout of the Arf gene alone provides no significant advantage for HSC/HPC expansion and self-renewal,16”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [16]
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- Authors
- Lessard, J., & Sauvageau, G.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Hôpital Maisonneuve-Rosemont (CA)
- Corresponding author
- Sauvageau, Guy
- Venue
- Nature
- Published
- 2003-04-20
- Volume
- 423
- Issue
- 6937
- Pages
- 255-260
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2092015913
- Cited by
- 1,452
- References
- 24
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 20 · 2022: 24 · 2021: 50 · 2020: 30 · 2019: 34 · 2018: 32 · 2017: 41 · 2016: 65 · 2015: 53 · 2014: 91 · 2013: 83 · 2012: 91
- FWCI
- 46.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Leukemia and Lymphoma Society
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- BMI1, Polycomb group genes, leukemia stem cells, normal stem cells, progenitor cells, cell proliferation, cancer stem cells, differentiation, apoptosis, complementation
- MeSH terms
- Animals, Cell Division, Clone Cells, Genotype, Leukemia, Liver, Neoplasm Transplantation, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, Stem Cells, Neoplastic Stem Cells, Gene Deletion, Mice, Polycomb Repressive Complex 1
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