title: Participation of the cytokines interleukin 6, tumor necrosis factor-alpha, and interleukin 1-beta secreted by acute myelogenous leukemia blasts in autocrine and paracrine leukemia growth control.
abstract: Autonomous in vitro growth of myeloid leukemic colony-forming cells may in part result from autocrine production of colony-stimulating factors (CSF). Some acute myeloid leukemia (AML) samples, however, fail to synthesize CSF despite growing autonomously in agar, and are therefore believed to bypass CSF requirements. Cytokines such as IL-6, tumor necrosis factor (TNF)-alpha, and IL-1, products of cells of the myeloid lineage, are known to be involved in growth control of myeloid progenitor cells. Since these molecules may also contribute to autocrine and paracrine growth regulation of myeloid leukemias, we screened a series of AML for cytokine production. In addition, possible roles of IL-6, TNF-alpha, and IL-1 in growth control of AML were investigated in vitro. We show that a substantial proportion of AML cells produce IL-6, TNF-alpha, and IL-1-beta and use these mediators to stimulate their growth by disparate mechanisms: IL-6 acts as a costimulator to enhance CSF-induced clonogenicity of AML blasts. TNF-alpha induces CSF production by endothelial cells and may therefore provide a paracrine loop to support leukemia growth.
authors: Department of Hematology, Johannes Gutenberg University, Mainz, Federal Republic of Germany.
authors: W
authors: W
authors: Oster
authors: N A
authors: NA
authors: Cicco
authors: H
authors: H
authors: Klein
authors: T
authors: T
authors: Hirano
authors: T
authors: T
authors: Kishimoto
authors: A
authors: A
authors: Lindemann
authors: R H
authors: RH
authors: Mertelsmann
authors: F
authors: F
authors: Herrmann
mesh_terms: D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha