Constitutive and induced expression of hematopoietic growth factor genes by fibroblasts from children with Fanconi anemia

G. C. Bagby, G. M. Segal, A. D. Auerbach, T. Onega, W. Keeble, M. C. Heinrich

    Research output: Contribution to journalArticle

    19 Scopus citations

    Abstract

    The pathophysiological abnormalities leading to marrow failure and leukemogenesis in children with Fanconi anemia (FA) are not understood. We tested the hypothesis that the Fanconi anemia mutation results in insufficient production of hematopoietic growth factors by stromal cells by quantifying constitutive and induced production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and steel factor (SF) by untransformed fibroblasts from eight patients with FA from five different families. While no abnormalities were noted in SF or M-CSF production, we noted substantial variability in IL-6, GM-CSF, and G-CSF responses of cells obtained from different FA patients. Responses ranged from blunting to augmentation when compared to normal controls. Because there was variation between fibroblast strains from affected members of two multiplex sibships, however, it is clear that neither augmentation nor blunting is a direct effect of the FA mutations. In addition, because there was discordance between the G-CSF responses and the GM-CSF and IL-6 responses, the abnormalities noted in IL-1 responsiveness must lie distal to IL-1 receptor function and to stimulus-response coupling pathways shared between the three cytokines.

    Original languageEnglish (US)
    Pages (from-to)1419-1426
    Number of pages8
    JournalExperimental hematology
    Volume21
    Issue number11
    StatePublished - Dec 1 1993

    Keywords

    • G-CSF
    • GM-CSF
    • Gene expression
    • Interleukin-1
    • Interleukin-6
    • M-CSF
    • Steel factor
    • Stromal cell

    ASJC Scopus subject areas

    • Molecular Biology
    • Hematology
    • Genetics
    • Cell Biology
    • Cancer Research

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