Aml1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes.
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.
Klymenko
Sergiy
S
Department of Haematology, Research Centre for Radiation Medicine, Kyiv, Ukraine. klymenko_sergiy@yahoo.co.uk
Trott
Klaus
K
Atkinson
Michael
M
Bink
Karin
K
Bebeshko
Vladimir
V
Bazyka
Dimitry
D
Dmytrenko
Iryna
I
Abramenko
Iryna
I
Bilous
Nadia
N
Misurin
Andrei
A
Zitzelsberger
Horst
H
Rosemann
Michael
M
D000328:Adult; D000368:Aged; D015984:Causality; D047852:Chernobyl Nuclear Accident; D050676:Core Binding Factor Alpha 2 Subunit; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D011210:Power Plants; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018788:Radioactive Hazard Release; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics / Q000528:radiation effects; D014455:Ukraine / Q000453:epidemiology
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors