Differentiation-inducing Effect of Recombinant Human Tumor Necrosis Factor a and γ-Interferon in Vitro on Blast Cells from Patients with Acute Myeloid Leukemia and Myeloid Blast Crisis of Chronic Myeloid Leukemia

Klaus Geissler, Guido Tricot, Tom Leemhuis, Edwin Walker, Hal E. Broxmeyer

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Tumor necrosis factor α (TNF-α) and γ-interferon (IFN-γ) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-α and IFN-γ are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemias (5 patients), it was found that recombinant human TNF-α and IFN-γ significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P < 0.001 and P < 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for α-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-α and IFN-γ significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-γ or TNF-α differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.

Original languageEnglish (US)
Pages (from-to)3057-3062
Number of pages6
JournalCancer Research
Volume49
Issue number11
StatePublished - Jun 1 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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