Complex Y chromosome aberrations are a recurrent secondary event in radiation-induced murine acute myeloid leukaemia.
Arbitrarily primed-PCR analysis of DNA from male CBA/H radiation-induced leukaemic spleens revealed the loss of an approximately 350-bp sequence in several leukaemias. We have isolated a lambda EMBL3 C57BL/6 genomic subclone (pJB1) which hybridizes to the AP-PCR probe and is located on the Y chromosome. Southern blot analyses using the pJB1 probe indicate that the genomic sequence was deleted in five of 14 leukaemias. Cytogenetic analyses of 31 X-ray induced leukaemias in male CBA/H mice revealed, in addition to the characteristic partial deletion of chromosome 2 (28/31 leukaemias), a high incidence (16/31) of the loss of an intact Y chromosome. Comparison of the Southern blot and cytogenetic analyses of the leukaemias demonstrate a significant lack of correspondence between the loss of an intact Y chromosome and Y chromosome-specific DNA sequences, suggesting that Y chromosome aberrations are complex. Whereas partial deletion of chromosome 2 can be detected in 6% of bone marrow cells within 6-11 days of irradiation, no Y chromosome involvement was detected, indicating that Y chromosome aberrations are a late event in radiation-induced leukaemogenesis. These findings are comparable to the loss of sex chromosomes in human t(8;21) AML.
Fennelly
J
J
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
Crabtree
G
G
Macdonald
D
D
Lorimore
S
S
Laval
S
S
Proffitt
J
J
Boyd
Y
Y
Wright
E
E
Plumb
M
M
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D016172:DNA Fingerprinting; D004273:DNA, Neoplasm / Q000235:genetics; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014998:Y Chromosome / Q000648:ultrastructure*
D004273:DNA, Neoplasm