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

J Radiat Res. 2005 Jun;46(2):249-55. doi: 10.1269/jrr.46.249.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Causality
  • Chernobyl Nuclear Accident*
  • Core Binding Factor Alpha 2 Subunit
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Incidence
  • Leukemia, Myeloid, Acute / epidemiology*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / epidemiology*
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism*
  • Neoplasms, Radiation-Induced / epidemiology*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / metabolism*
  • Power Plants
  • Proto-Oncogene Proteins / genetics*
  • Radioactive Hazard Release
  • Risk Assessment / methods
  • Risk Factors
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics
  • Translocation, Genetic / radiation effects
  • Ukraine / epidemiology

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Transcription Factors