The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.
|Number of pages||9|
|Publication status||Published - Oct 2013|
Bibliographical noteFunding Information:
Financial support was provided by the National Institute for Health Research Centre for Research in Public Health Protection at the Health Protection Agency and by the European Union FP7 DoReMi network of excellence (Grant number 249689 ). The authors alone are responsible for the content and writing of the paper. This report is work commissioned by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessary those of the NHS, the National Institute for Health Research or the department of Health.
- Chromosome deletion
- Live cells
- Mouse model
- Myeloid leukaemia