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Several studies suggested a causal link between AML1 gene rearrangements and both radiation-induced acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Fifty-three AML samples were analyzed for the presence of AML1 abnormalities using fluorescent in-situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR). Of these patients, 24 had experienced radiation exposure due to the Chernobyl accident, and 29 were non-irradiated spontaneous AML cases and served as controls. AML1/ETO translocations were found in 9 of 29 spontaneous AML but only in 1 of 24 radiation-associated AML cases. This difference between translocation frequencies is statistically significant in the age-unstratified cohorts (p=0.015). Following age stratification, the difference becomes less pronounced but remains on borderline significance (p=0.053). AML1 mutation status was assessed in 5 clean-up workers at Chernobyl NPP with MDS, or AML following MDS, by direct sequencing of genomic DNA from the coding region (exon 3 through 8). In one patient who developed MDS following an acute radiation syndrome, a hexanucleotide duplication of CGGCAT in exon 8 was found, inserted after base position 1502. Our results suggest that AML1 gene translocations are infrequent in radiation-induced leukemogenesis but are consistent with the idea that radiation may contribute to the development of MDS through AML1 gene mutation.

Aim: Although acute myelogenous leukemia (AML) arising after radiation exposure is considered to be secondary, little is known about the molecular mechanisms by which the radiation induces the leukemogenic phenotype. The aim of the study was to analyze whether the MLL translocations are as frequent in radiation-associated AML as in spontaneous AML cases. Methods: Sixty one AML samples obtained at diagnosis were analyzed for the presence of MLL abnormalities using fluorescent in situ hybridization and/or reverse transcription polymerase chain reaction. Of these patients, 27 had experienced radiation exposure due to the Chernobyl accident, 32 were non-irradiated (spontaneous AML), and 2 developed therapy-related AML after chemotherapy with topoisomerase II inhibitors. Results: MLL gene translocations were detected in both groups of spontaneous and therapy-related AML (1/32 and 1/2 cases respectively). The sole MLL rearrangement found in the group of radiation-associated AML patients was a duplication of the gene. Conclusion: Our data preclude the involvement of MLL gene translocations in radiation-induced leukemogenesis, but support the assumption that loss and gain of chromosomal material could be crucial in the leukemogenesis of AML patients with the history of radiation exposure due to the Chernobyl accident.