The SJL/J mouse strain has a high spontaneous incidence of a B-cell
neoplasm, reticulum cell
neoplasm type B (RCN B). In addition, following irradiation, 10% to 30% of these mice develop
acute myelomonocytic leukemia (radiation-induced
acute myeloid leukemia [RI-AML]), an incidence that can be increased to 50% by treatment of the mice with
corticosteroids after irradiation. The role played by the mononuclear phagocyte
growth factor, colony-stimulating factor-1 (CSF-1), in the development of RI-AML in SJL/J mice was investigated. Mice dying of RI-AML, but not those dying of RCN B or without disease, possessed elevated concentrations of circulating
CSF-1. In addition, in mice developing RI-AML with a more prolonged latency, circulating
CSF-1 concentrations were increased before overt expression of RI-AML. First-passage
tumors from 14 different RI-AMLs all contained high concentrations of
CSF-1, and six of six different first- or second-passage
tumors expressed the
CSF-1 receptor (CSF-1 R). Furthermore, in vitro colony formation by first- or second-passage
tumor cells from 20 of 20 different RI-AMLs was blocked by neutralizing anti-CSF-1 antibody, and four of four of these
tumors were inhibited by anti-CSF-1R antibody. The results of these antibody neutralization studies, coupled with the observation of elevated circulating
CSF-1 in mice developing RI-AML, show an autocrine role for
CSF-1 in RI-AML development in SJL/J mice. Southern blot analysis of
tumor DNA from six of six of these
tumors failed to reveal any rearrangements in the genes for
CSF-1 or the CSF-1R. Studies in humans have shown that patients with AML possess elevated levels of circulating
CSF-1 and that AML cells can express
CSF-1 and the CSF-1R. Thus, RI-AML in the SJL/J mouse appears to be a useful model for human AML.