MLL gene alterations in radiation-associated acute myeloid leukemia.
OBJECTIVE
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.


CONCLUSIONS
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.
Klymenko
Sergiy V
SV
Research Centre for Radiation Medicine, Academy of Medical Science of Ukraine, Kyiv 04050, Ukraine. klymenko_sergiy@yahoo.co.uk
Bink
Karin
K
Trott
Klaus R
KR
Bebeshko
Vladimir G
VG
Bazyka
Dimitry A
DA
Dmytrenko
Iryna V
IV
Abramenko
Iryna V
IV
Bilous
Nadia I
NI
Zitzelsberger
Horst
H
Misurin
Andrei V
AV
Atkinson
Michael J
MJ
Rosemann
Michael
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047852:Chernobyl Nuclear Accident; D002869:Chromosome Aberrations / Q000139:chemically induced / Q000528:radiation effects*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase