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Increased circulating colony-stimulating factor-1 (CSF-1) in SJL/J mice with radiation-induced acute myeloid leukemia (AML) is associated with autocrine regulation of AML cells by CSF-1.

Abstract
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.
AuthorsN Haran-Ghera, R Krautghamer, T Lapidot, A Peled, M G Dominguez, E R Stanley
JournalBlood (Blood) Vol. 89 Issue 7 Pg. 2537-45 (Apr 1 1997) ISSN: 0006-4971 [Print] UNITED STATES
PMID9116300 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Neoplasm Proteins
  • Dexamethasone
  • Macrophage Colony-Stimulating Factor
Topics
  • Acute Disease
  • Animals
  • Cell Division
  • Dexamethasone (toxicity)
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Humans
  • Leukemia, Myeloid (blood, etiology)
  • Leukemia, Radiation-Induced (blood)
  • Lymphoma, Large B-Cell, Diffuse (blood, genetics)
  • Macrophage Colony-Stimulating Factor (blood, secretion)
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Proteins (blood, secretion)
  • Neoplastic Stem Cells (pathology, secretion)
  • Tumor Cells, Cultured
  • Whole-Body Irradiation (adverse effects)

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