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Klymenko, S.* ; Trott, K.* ; Atkinson, M.J. ; Bink, K. ; Bebeshko, V.* ; Bazyko, D.* ; Dmytrenko, I.* ; Abramenko, I.* ; Bilous, N.* ; Misurin, A.* ; Zitzelsberger, H.

Aml1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes.

J. Radiat. Res. 46, 249-255 (2005)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Acute Myeloid Leukaemia ; Aml1 ; Chernobyl Accident ; Ionizing Radiation ; Myelodysplastic Syndromes; IONIZING-RADIATION; CHERNOBYL ACCIDENT; AML1/PEBP2-ALPHA-B GENE; SOMATIC MUTATIONS; POINT MUTATIONS; RUNT DOMAIN; MALIGNANCIES; COUNTRIES; FALLOUT; WORKERS
ISSN (print) / ISBN 0449-3060
e-ISSN 1349-9157
Quellenangaben Volume: 46, Issue: 2, Pages: 249-255 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Radiation Biology (IMS)
Institute of Pathology (PATH)