A major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia.
Cytogenetic and molecular studies have provided evidence of the clustering of chromosome 2 deletion breakpoints in radiation-induced murine acute myeloid leukemia (AML). Moreover, clustering occurs in at least two fragile domains rich in telomere-like arrays. Here we describe a physical map of the distal breakpoint cluster and confirm the presence of inverted head-to-head telomeric sequence arrays. These potentially recombinogenic sequences were not, however, the direct focus for post-irradiation chromosome breakage in AML. Instead, the two arrays bordered a 2.5-kb sequence with properties expected of a nuclear matrix attachment region (MAR). The putative MAR co-localized in the fragile domain with genes important to the hemopoietic system (leukocyte tyrosine kinase, zinc finger protein 106, erythrocyte protein band 4.2, and beta(2)-microglobulin (beta2m)); the beta2m subdomain was a particular focus of breakage. On the basis of these and other data, we suggest that AML-associated chromosome 2 fragility in the mouse is a consequence of domain-specific fragility in genomic domains containing numerous genes critical to the hemopoietic system. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by Wiley-Liss, Inc.
Radiation Effects Department, National Radiological Protection Board, Chilton, England.
Rosemary
R
Finnon
John
J
Moody
Emmy
E
Meijne
Jackie
J
Haines
Debbie
D
Clark
Alan
A
Edwards
Roger
R
Cox
Andrew
A
Silver
D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D018244:Chromosomes, Artificial, Yeast; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
D004273:DNA, Neoplasm