INCREASED CIRCULATING COLONY-STIMULATING FACTOR-I (CSF-1) IN SJL J MICE WITH RADIATION-INDUCED ACUTE MYELOID-LEUKEMIA (AML) IS ASSOCIATED WITH AUTOCRINE REGULATION OF AML CELLS BY CSF-1/

The SJL/J mouse strain has a high spontaneous incidence of a B-cell ne oplasm, reticulum cell neoplasm type B (RCN B). In addition, following irradiation, 10% to 30% of these mice develop acute myelomonocytic le ukemia (radiation-induced acute myeloid leukemia [RI-AML]), an inciden ce that can be increased to 50% by treatment of the mice with corticos teroids after irradiation. The role played by the mononuclear phagocyt e growth factor, colony-stimulating factor-1 (CSF-1), in the developme nt 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 conce ntrations 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-1R). Furthermore, in vitro colony formation by first- or second-passage tumor cells from 20 of 20 different RI-AMLs was blo cked by neutralizing anti-CSF-1 antibody, and four of four of these tu mors were inhibited by anti-CSF-1R antibody. The results of these anti body neutralization studies, coupled with the observation of elevated circulating CSF-1 in mice developing RI-AML, show an autocrine role fo r 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 rearra ngements in the genes for CSF-1 or the CSF-1R. Studies in humans have shown that patients with AML possess elevated levels of circulating CS F-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. (C) 199 7 by The American Society of Hematology.