Abstract
Murine 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, for instance by G-banding. For its rapid diagnosis, we report FISH analysis of spleen cells and peripheral blood smears of ML mice exposed to gamma ray and neutrons using a probe of PU.1, a candidate for an ML tumor suppressor.
Among mice that were tentatively diagnosed with ML by clinical findings and blood smear examination, 85% carried spleen cells showing one loss of PU.1 although the frequency of these abnormal cells varied among individuals. Mice with very low frequencies of cells showing one loss of PU.1 (one-PU.1 frequency) were later diagnosed pathologically with not ML but 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 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).
The FISH method to detect aberration of the PU.1 gene on murine chromosome 2 using a peripheral blood smear is more practical and less invasive than conventional pathological diagnosis and for cytogenetic examination of spleen cells.
