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

Nechama Haran-Ghera, Rita Krautghamer, Tsvee Lapidot, Alpha Peled, Melissa G. Dominguez, E. Richard Stanley

Research output: Contribution to journalArticle

21 Citations (Scopus)

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-1R). 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.

Original languageEnglish (US)
Pages (from-to)2537-2545
Number of pages9
JournalBlood
Volume89
Issue number7
StatePublished - Apr 1 1997

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Macrophage Colony-Stimulating Factor
Myeloid Cells
Acute Myeloid Leukemia
Radiation
Tumors
Macrophage Colony-Stimulating Factor Receptors
Neoplasms
Reticulum
Antibodies
Colony-Stimulating Factor Receptors
Cells
Leukemia, Myelomonocytic, Acute
Irradiation
Gene Rearrangement
Incidence
Phagocytes
Southern Blotting
Intercellular Signaling Peptides and Proteins
Adrenal Cortex Hormones
B-Lymphocytes

ASJC Scopus subject areas

  • Hematology

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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. / Haran-Ghera, Nechama; Krautghamer, Rita; Lapidot, Tsvee; Peled, Alpha; Dominguez, Melissa G.; Stanley, E. Richard.

In: Blood, Vol. 89, No. 7, 01.04.1997, p. 2537-2545.

Research output: Contribution to journalArticle

Haran-Ghera, Nechama ; Krautghamer, Rita ; Lapidot, Tsvee ; Peled, Alpha ; Dominguez, Melissa G. ; Stanley, E. Richard. / 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. In: Blood. 1997 ; Vol. 89, No. 7. pp. 2537-2545.
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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-1R). 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.",
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AU - Krautghamer, Rita

AU - Lapidot, Tsvee

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AU - Dominguez, Melissa G.

AU - Stanley, E. Richard

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