Opposite effect of tumor necrosis factor α on granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor-dependent growth of normal and leukemic hemopoietic progenitors

W. Piacibello, F. Sanavio, A. Severino, S. Morelli, A. M. Vaira, A. Stacchini, M. Aglietta

Research output: Contribution to journalArticle

Abstract

The effect of recombinant human tumor necrosis factor α (TNF-α) on normal and chronic myeloid leukemia granulocyte-macrophage progenitors (CFU-GM) growing in semisolid agar cultures in the presence of recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor was studied. Granulocyte-macrophage colony-stimulating factor-dependent growth of normal and chronic myeloid leukemia bone marrow CFU-GM was greatly enhanced by TNF-α at doses of 0.1 to 100 units/ml. Growth enhancement included neutrophil, eosinophil, and monocyte-macrophage colonies and clusters at 7 and 14 days of culture. Since similar results were achieved with highly enriched progenitor cell populations, devoid of accessory cells, an indirect effect on CFU-GM growth through the release by accessory cells of other cytokines upon TNF-α stimulation was thus ruled out. By contrast, the same doses of TNF-α inhibited the growth of normal CFU-GM in granulocyte colony-stimulating factor-dependent cultures. Taken together, our findings indicate that the final effect of TNF-α on normal bone marrow granulocyte-macrophage progenitor growth is dependent on the specific growth factor interacting with it, and that both normal and chronic myeloid leukemia CFU-GM are equally responsive to the combined effects of TNF-α and a given colony-stimulating factor.

Original languageEnglish
Pages (from-to)5065-5071
Number of pages7
JournalCancer Research
Volume50
Issue number16
Publication statusPublished - 1990

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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