MICROSATELLITE ANALYSIS OF RECURRENT CHROMOSOME-2 DELETIONS IN ACUTE MYELOID-LEUKEMIA INDUCED BY RADIATION IN FI HYBRID MICE

Deletions and/or rearrangements involving one copy of chromosome 2 are consistent and early events in the development of murine acute myeloi d leukaemia (AML) by radiation. More than 90% of AMLs induced in the C BA strain of mice express such cytogenetic alterations, with chromosom e 2 breakpoints clustering in the C and F regions of the chromosome. I n inbred mouse strains, the molecular resolution of these breakpoints is problematic. However, by using x-ray-induced AMLs in FI progeny of genetically divergent CBA/H x C57BI, it has been possible to show regi on-specific loss of heterozygosity (LOH) in genetically linked sets of chromosome 2 microsatellite alleles from one of the two parental chro mosomes. In the majority of cases, an acceptable concordance was shown for AML chromosome 2 deletion, as defined by microsatellites and as r evealed by G-band cytogenetics. A degree of breakpoint clustering was found, but the identification of a number of deletion types, based on the position of proximal and distal breakpoints as defined by microsat ellite analysis, strongly supports a leukaemogenic mechanism involving gene deletion. No bias towards loss of CBA or C57BI alleles was obser ved, and the gender of AML-presenting animals did not appear to influe nce the parental origin of the deletions. A molecular map of chromosom e 2 breakpoints has now been established in Fl AMLs as a first step to wards the molecular cloning of breakpoint sequences. (C) 1996 Wiley-Li ss, Inc.