Specificity of loss of heterozygosity in radiation-induced mouse myeloid and lymphoid leukaemias

Purpose: To determine whether loss of heterozygosity (LOH) at specific chro mosomal loci in radiation-induced leukaemias, arising in a similar genetic background, is leukaemia-type specific (myeloid versus lymphoid) or common to both. Materials and methods: Leukaemias that arose in 3 Gy X-irradiated (CBA/H x C57BL/6)F1 intercross and backcross mice were diagnosed as acute myeloid le ukaemia (AML) or thymic lymphoma (TL). LOH was determined using 28 polymorp hic microsatellite markers distributed over seven chromosomes using control and leukaemic DNA from individual mice. Results: LOH incidences of 0-20% were observed at most loci in both leukaem ia types. Specific LOH incidences of 38-76% were observed for myeloid (chro mosome 2) and lymphoid (chromosomes 11 and 14) leukaemias. Chromosome 4 LOH was frequently (38-50%) observed in both types, although the commonly dele ted regions differed. LOH was detected at either chromosome 2 or 4 in AML a nd either chromosome 4 or 11 in TL. Conclusions: LOH incidences of 38-76% suggest a causal role of particular l oci which is mainly, but not exclusively, dependent on leukaemia type. LOH incidences of 0-20% at other loci in both leukaemias suggest that many gene tic deletions are noncausal and incidental in radiation-leukaemogenesis.