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FJ Bot, P Schipper, L Broeders, R Delwel, K Kaushansky and B Lowenberg
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
The cytokine interleukin-1 (IL-1) plays a role in the regulation of normal
as well as leukemic hematopoiesis. In acute myeloid leukemia (AML), IL-1
induces autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF)
and tumor necrosis factor (TNF) production, and these factors may then
synergistically induce proliferation in AML blast cells. In this report, we
show that IL-1 stimulates DNA synthesis of highly enriched normal bone
marrow blast cells (CD34 positive, adherent cell depleted, CD3/CD14/CD15
negative). The stimulative effect of IL-1 can be blocked with neutralizing
anti-TNF alpha and anti-GM-CSF antibodies and, most efficiently, by the
combination of anti-TNF alpha and anti-GM-CSF, but not with anti-G-CSF
antibody, suggesting that IL-1- induced proliferation was initiated through
TNF and GM-CSF release. Concentrations of TNF and GM-CSF increased in the
culture medium of normal bone marrow blast cells after IL-1 induction. Of
the IL-1- induced cells, 12% were positive for GM-CSF mRNA by in situ
hybridization, as opposed to 6% of non-induced cells. Thus, in addition to
its effect on leukemic blast cells, IL-1 also acts on normal marrow blast
cells. We propose a scheme where IL-1 stimulation of normal bone marrow
blast cells leads to the induction of TNF alpha and GM-CSF, which in
association stimulate DNA synthesis efficiently according to a paracrine or
autocrine mechanism within the marrow blast cell compartment.
This article has been cited by other articles:
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
