Rapid and reliable diagnosis of murine myeloid leukemia (ML) by FISH of peripheral blood smear using probe of PU. 1, a candidate ML tumor suppressor

Abstract

BackgroundMurine myeloid leukemia (ML) provides a good animal model to study the mechanisms of radiation-induced leukemia in humans. This disease has been cytogenetically characterized by a partial deletion of chromosome 2 with G-banding. For the rapid diagnosis of ML, this study reports a FISH method using spleen cells and peripheral blood smears from ML mice exposed to gamma rays and neutrons with PU.1, a candidate ML tumor suppressor, as a probe.ResultsAmong mice that were tentatively diagnosed with ML by clinical findings and blood smear examination, 85% carried spleen cells showing the loss of PU.1 although the frequency of these abnormal cells varied among individuals. Mice with very low frequencies of cells showing the loss of one copy of PU.1 (one-PU.1 frequency) were later diagnosed pathologically not with ML but with blastic or eosinophilic leukemia. Some neutron-irradiated mice had cells showing translocated PU.1, although no pathological features differentiated these ML mice from ML mice expressing the simple loss of PU.1.The one-PU.1 frequency can be detected from spleen metaphase cells, spleen interphase cells, and blood smears. There was a good correlation between the one-PU.1 frequency in spleen metaphase cells and that in spleen interphase cells (r = 0.96) and between one-PU.1 frequency in spleen interphase cells and that in blood cells (r = 0.83).ConclusionThe FISH method was capable of detecting aberration of copy number of the PU.1 gene on murine chromosome 2, and using a peripheral blood smear is more practical and less invasive than conventional pathological diagnosis or the cytogenetic examination of spleen cells.

No Evidence for the in vivo Induction of Genomic Instability by Low Doses of 137Cs Gamma Rays in Bone Marrow Cells of BALB/cJ and C57BL/6J Mice

“…Similar findings of the hypermutability of mouse chr2 following exposure to low LET radiation have also been described by other groups of investigators (Ban et al 1997; Bouffler et al 1997; Xiao et al 1999). Further, chr2 lesions have been well recognized to be an important genetic event in the development of radiation-induced myeloid leukemia (rML) (Hayata et al 1979; Cox et al 1991; Bouffler et al 1996; Ban et al 1997; Rithidech et al 1999; Xiao et al 1999; MacDonald et al 2001; Jawad et al 2006; Kanda et al 2008; Peng et al 2009). However, it is possible that the lesions on mouse chr2 acquired in rML cells may not be the lesions that are responsible for the induction of genomic instability in exposed cells at early time post-irradiation.…”