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

BACKGROUND: 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 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. RESULTS: Among 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). CONCLUSION: The 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.