Frequency of acute myeloid leukaemia-associated mouse chromosome 2 deletions in X-ray exposed immature haematopoietic progenitors and stem cells
| Autor: | Natalie Brown, Simon Bouffler, Rosemary Finnon, Christophe Badie, C.-H. Olme |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lin−
lineage negative immature bone marrow cells Sfpi1/PU.1 Health Toxicology and Mutagenesis 7-AAD 7-aminoactinomycin D Stem cells Mice chemistry.chemical_compound 0302 clinical medicine Bone Marrow Antigens Ly Cells Cultured In Situ Hybridization Fluorescence GFP green fluorescent protein Colony-forming unit 0303 health sciences education.field_of_study Radiation 7-Aminoactinomycin D del2 interstitial deletion of chromosome 2 Flow Cytometry 3. Good health Chromosome deletion Leukemia Myeloid Acute Proto-Oncogene Proteins c-kit Haematopoiesis medicine.anatomical_structure 030220 oncology & carcinogenesis Sfpi1GFP/GFP homozygous for the Sfpi1-GFP reporter gene Stem cell CMP common myeloid progenitor Green Fluorescent Proteins Population BMCs bone marrow cells LSK Lin− Sca-1+ c-Kit+ Biology Article rAML radiation-induced acute myeloid leukaemia Chromosomes Sfpi1GFP/+ heterozygous for the Sfpi1-GFP reporter gene Mouse model 03 medical and health sciences Cancer stem cell medicine Genetics Animals Cell Lineage Progenitor cell MMP multi-potent progenitor education CFU-S12 colony forming unit spleen on day 12 030304 developmental biology IR ionising radiation Immunomagnetic Separation X-Rays IMDM Iscove's modified Dulbecco's medium Membrane Proteins Hematopoietic Stem Cells CSC cancer stem cell Molecular biology Mice Inbred C57BL chemistry BAC-FISH bacterial artificial chromosome-fluorescent in situ hybridisation MEP myeloid-erythroid progenitor Myeloid leukaemia Mice Inbred CBA HSC haematopoietic stem cell Bone marrow |
| Zdroj: | Mutation Research |
| ISSN: | 1383-5718 |
| DOI: | 10.1016/j.mrgentox.2013.04.018 |
| Popis: | Exposure to ionising radiation can lead to an increased risk of cancer, particularly leukaemia. In radiation-induced acute myeloid leukaemia (rAML), a partial hemizygous deletion of mouse chromosome 2 is a common feature in several susceptible strains. The deletion is an early event detectable 24h after exposure in bone marrow cells using cytogenetic techniques. Expanding clones of bone marrow cells with chromosome 2 deletions can be detected less than a year after exposure to ionising radiation in around half of the irradiated mice. Ultimately, 15-25% of exposed animals develop AML. It is generally assumed that leukaemia originates in an early progenitor cell or haematopoietic stem cell, but it is unknown whether the original chromosome damage occurs at a similar frequency in committed progenitors and stem cells. In this study, we monitored the frequency of chromosome 2 deletions in immature bone marrow cells (Lin(-)) and haematopoietic stem cells/multipotent progenitor cells (LSK) by several techniques, fluorescent in situ hybridisation (FISH) and through use of a reporter gene model, flow cytometry and colony forming units in spleen (CFU-S) following ex vivo or in vivo exposure. We showed that partial chromosome 2 deletions are present in the LSK subpopulation, but cannot be detected in Lin(-) cells and CFU-S12 cells. Furthermore, we transplanted irradiated Lin(-) or LSK cells into host animals to determine whether specific irradiated cell populations acquire an increased proliferative advantage compared to unirradiated cells. Interestingly, the irradiated LSK subpopulation containing cells carrying chromosome 2 deletions does not appear to repopulate as well as the unirradiated population, suggesting that the chromosomal deletion does not provide an advantage for growth and in vivo repopulation, at least at early stages following occurrence. |
| Databáze: | OpenAIRE |
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