Aml1 Gene Rearrangements and Mutations in Radiation-Associated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Sergiy Klymenko; Klaus TROTT; Michael ATKINSON; Karin BINK; Vladimir BEBESHKO; Dimitry BAZYKA; Iryna DMYTRENKO; Iryna ABRAMENKO; Nadia BILOUS; Andrei MISURIN; Horst Zitzelsberger; Michael Rosemann

doi:10.1269/jrr.46.249

Regular Papers

Aml1 Gene Rearrangements and Mutations in Radiation-Associated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Sergiy Klymenko, Klaus TROTT, Michael ATKINSON, Karin BINK, Vladimir BEBESHKO, Dimitry BAZYKA, Iryna DMYTRENKO, Iryna ABRAMENKO, Nadia BILOUS, Andrei MISURIN, Horst Zitzelsberger, Michael Rosemann

Author information

Sergiy Klymenko
Department of Haematology, Research Centre for Radiation Medicine
Klaus TROTT
Gray Cancer Institute, P.O. Box 100, Mount Vernon Hospital
Michael ATKINSON
Institute of Pathology, National Research Center for Environment and Health
Karin BINK
Institute of Pathology, National Research Center for Environment and Health
Vladimir BEBESHKO
Department of Haematology, Research Centre for Radiation Medicine
Dimitry BAZYKA
Department of Haematology, Research Centre for Radiation Medicine
Iryna DMYTRENKO
Department of Haematology, Research Centre for Radiation Medicine
Iryna ABRAMENKO
Department of Haematology, Research Centre for Radiation Medicine
Nadia BILOUS
Department of Haematology, Research Centre for Radiation Medicine
Andrei MISURIN
Hematology Research Centre
Horst Zitzelsberger
Institute of Molecular Biology, National Research Center for Environment and Health
Michael Rosemann
Institute of Pathology, National Research Center for Environment and Health

Keywords: AML1, Acute myeloid leukaemia, Myelodysplastic syndromes, Ionizing radiation, Chernobyl accident

JOURNAL FREE ACCESS

2005 Volume 46 Issue 2 Pages 249-255

DOI https://doi.org/10.1269/jrr.46.249

Details

Abstract

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.

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