A major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia
✍ Scribed by Rosemary Finnon; John Moody; Emmy Meijne; Jackie Haines; Debbie Clark; Alan Edwards; Roger Cox; Andrew Silver
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 170 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.10054
No coin nor oath required. For personal study only.
✦ Synopsis
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.