Selective Induction of Leukemia-associated Fusion Genes by High-Dose Ionizing Radiation

摘要: Abstract There is strong clinical and epidemiological evidence that ionizing radiation can cause leukemia by inducing DNA damage. This crucial initiation event believed to be the result of random breakage misrepair, whereas subsequent steps, promotion progression, must rely on mechanisms selective pressure provide expanding leukemic population with its proliferative/renewal advantage. To investigate susceptibility human cells external agents at genetic recombination stage leukemogenesis, we subjected two hematopoletic cell lines, KG1 HL60, high doses γ-irradiation. The irradiation induced formation fusion genes characteristic in both but a much higher frequency than HL60. In cells, AML1-ETO hybrid gene [associated t(8;21) translocation acute myeloid leukemia] occurred significantly more often BCR-ABL t(9;22) chronic or DEK-CAN t(6;9) genes. These findings support notion directly generate leukemia-specific emphasize differing different populations which various are formed. selectivity observed primary level may explain least part differential risk for development some not other forms after high-dose exposure.