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Objective: The objective of this study was to delineate a precise molecular map of the commonly deleted region (CDR) on mouse chr2 in radiation-induced mouse acute myeloid leukemic (AML) cells., Materials and Methods: We used a PCR-based loss of heterozygosity (LOH) assay to map the chr2-CDR in AML cells isolated from F1 hybrid mice (BALB/cJ x CBA/CaJ) which developed AML following exposure to a single dose of 3 Gy of 137Cs gamma rays. A total of 30 polymorphic microsatellite markers, mapping within or close to chr2(D-E), were used under optimized PCR conditions that generate a single major band for each marker on a nondenaturing polyacrylamide gel., Results: Detailed LOH mapping identified two distinct AML-CDRs: one localized to a 4.6 centiMorgan (cM) interval between markers D2Mit272 and D2Mit394; the other mapped to a 0.8 cM interval between markers D2Mit276 and D2Mit444. Both CDRs span the mouse chr2E region., Conclusion: The data present, for the first time, evidence for two distinctly noncontiguous CDRs on mouse chr2 harboring gene(s) involved in AML development. These CDRs are orthologous to human chromosomes 11p11-13 and 15q11-15 that have been implicated in subsets of AML. This finding indicates the region of mouse chr2 that must be searched for candidate genes involved in radiation-induced AML.

G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcinogenesis, in which mice were exposed to radiation of several different qualities, i.e., x-rays, gamma-rays and "monoenergetic" fast neutrons of 5 mean energies ranging from 0.2 to 14 MeV. The 14 ML cases showed no histologically phenotypic differences and they were transplantable in syngeneic mice. We detected a specific chromosomal deletion in 1 copy of mouse chromosome 2 at regions D-E in all radiation-induced ML cells, regardless of radiation quality. Our results strongly implicate the involvement of genes within or close to regions D-E of chromosome 2 in radiation leukemogenesis. In addition to the specific deletion in chromosome 2, loss or gain of the Y chromosome was also detected in some cells from 6 ML cases. Because this hypo- or hyperploidy occurred in only a small fraction of leukemic cells, a causative role in radiation leukemogenesis appears unlikely.