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.
Department of Haematology, Research Centre for Radiation Medicine, Kyiv, Ukraine. klymenko_sergiy@yahoo.co.uk
Sergiy
S
Klymenko
Klaus
K
Trott
Michael
M
Atkinson
Karin
K
Bink
Vladimir
V
Bebeshko
Dimitry
D
Bazyka
Iryna
I
Dmytrenko
Iryna
I
Abramenko
Nadia
N
Bilous
Andrei
A
Misurin
Horst
H
Zitzelsberger
Michael
M
Rosemann
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