Chromosomal mechanisms in murine radiation acute myeloid leukaemogenesis.
Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-irradiation events in bone marrow cells in vivo and of karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2;11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore, two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal translocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis.
Bouffler
S D
SD
Biomedical Effects Department, National Radiological Protection Board, Didcot, Oxon, UK.
Breckon
G
G
Cox
R
R
D000208:Acute Disease; D000818:Animals; D002869:Chromosome Aberrations; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D051379:Mice; D008808:Mice, Inbred CBA; D013045:Species Specificity