The suppressive effects of recombinant human tumor necrosis factor‐alpha on normal and malignant myelopoiesis: Synergism with interferon‐gamma

Abstract

The modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor‐alpha (TNFα) and recombinant human interferon‐gamma (IFNγ) was investigated.TNFα inhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast‐type colonies derived from patients with acute myelogenous leukemia were more sensitive to TNFα inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable‐phase chronic myelogenous leukemia. The response of most colony types to IFNγ was poor. However, when IFNγ was administered together with TNFα, synergistically enhanced antiproliferative effects were detected in all colony types tested. The antiproliferative action of IFNγ on myelopoiesis was enhanced in culture by the presence of autologous monocytes, presumedly by inducing endogenous production of TNFα. However, TNFα seemed to act directly on the progenitor cells themselves to suppress their clonal growth, rather than involving accessory marrow elements such as monocytes and/or T lymphocytes.