A major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia

Rosemary Finnon, John Moody, Emmy Meijne, Jacqueline Haines, Debbie Clark, Alan Edwards, Roger Cox, Andrew Silver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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 β2-microglobulin (β2m)); the β2m 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.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalMolecular Carcinogenesis
Volume34
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Acute myeloid leukemia
  • Breakpoint cluster
  • Matrix attachment region
  • Mouse
  • Radiation
  • Telomere

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