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

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 leukemia (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.