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A PCR-based clonal analysis of radiation-induced loss of heterozygosity in haemopoietic stem cells

Leukemia volume 15, pages 1604–1611 (2001)Cite this article

Abstract

CBA mouse strains have been used for many years as a model of radiation-induced acute myeloid leukaemia and the leukaemias in CBA and their F1 hybrids are characterised by a specific loss of heterozygosity involving one homologue of chromosome 2. Previous cytogenetic studies of transplanted irradiated bone marrow, or of bone marrow obtained from irradiated mice significantly before the appearance of leukaemia, have been interpreted as the chromosome 2 deletion being a high frequency, possibly initiating event. However, these studies had not specifically addressed the question of whether the characteristic deletion was induced at a high frequency in stem cells. Using a PCR-based technique, we have studied the induction of chromosome 2 LOH in the progeny of (CBA/H × C57BL/6)F1 stem cells after a potentially leukaemogenic radiation exposure. Whilst chromosome 2 LOH can be induced directly by irradiation and there is a preferential loss of the CBA allele, the frequency is no greater than LOH induced in other chromosomal regions studied. The data do not support radiation-induced deletion involving one homologue of chromosome 2 in long-term repopulating stem cells (<1 in 200) being as high a frequency event as might be inferred by previous cytogenetic studies of total bone marrow.

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Acknowledgements

This work was supported by a specialist programme in Radiation Leukaemogenesis from the Leukaemia Research Fund (SP 9923) and MRC programme grant (G 9824583). We thank the staff of the biological services of the MRC Unit in Harwell (Oxfordshire).

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Authors and Affiliations

  1. Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

    BA Rigat, SA Lorimore & EG Wright

  2. Department of Genetics, University of Leicester, Leicester, UK

    MA Plumb

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  1. BA Rigat
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  2. SA Lorimore
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  3. MA Plumb
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  4. EG Wright
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Rigat, B., Lorimore, S., Plumb, M. et al. A PCR-based clonal analysis of radiation-induced loss of heterozygosity in haemopoietic stem cells. Leukemia 15, 1604–1611 (2001). https://doi.org/10.1038/sj.leu.2402237

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