MLL gene alterations in radiation-associated acute myeloid leukemia

Exp Oncol. 2005 Mar;27(1):71-5.

Abstract

Aim: Although acute myelogenous leukemia (AML) arising after radiation exposure is considered to be secondary, little is known about the molecular mechanisms by which the radiation induces the leukemogenic phenotype. The aim of the study was to analyze whether the MLL translocations are as frequent in radiation-associated AML as in spontaneous AML cases.

Methods: Sixty one AML samples obtained at diagnosis were analyzed for the presence of MLL abnormalities using fluorescent in situ hybridization and/or reverse transcription polymerase chain reaction. Of these patients, 27 had experienced radiation exposure due to the Chernobyl accident, 32 were non-irradiated (spontaneous AML), and 2 developed therapy-related AML after chemotherapy with topoisomerase II inhibitors.

Results: MLL gene translocations were detected in both groups of spontaneous and therapy-related AML (1/32 and 1/2 cases respectively). The sole MLL rearrangement found in the group of radiation-associated AML patients was a duplication of the gene.

Conclusion: Our data preclude the involvement of MLL gene translocations in radiation-induced leukemogenesis, but support the assumption that loss and gain of chromosomal material could be crucial in the leukemogenesis of AML patients with the history of radiation exposure due to the Chernobyl accident.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Chernobyl Nuclear Accident*
  • Chromosome Aberrations / chemically induced
  • Chromosome Aberrations / radiation effects*
  • DNA, Neoplasm / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid / etiology
  • Leukemia, Myeloid / genetics*
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein
  • Proto-Oncogenes / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*

Substances

  • DNA, Neoplasm
  • DNA-Binding Proteins
  • KMT2A protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase