CSF-1 and immune interferon synergize to induce differentiation of human leukemic cells bearing CSF-1 receptors

Abstract

Human promyelocytic leukemia cells (HL-60) expressing the colony-stimulating factor-1 (CSF-1) receptor either by γ-interferon (IFN) induction or genetic manipulation may be terminally differentiated after a long-term treatment with IFN and CSF-1. The differentiated cells obtained resemble their normal counterparts by exhibiting a highly granulated eosinophilic and basophilic cytoplasm which occupies most of the cell surface area and do not incorporate 3H-TdR as the untreated cells do. The combination of IFN and CSF-1 appears to be necessary for keeping these cells alive in culture. The percentage of the cells that can be driven to proliferative senescence can be as high as 50% and require a long treatment period ranging from 20 days to 2 months depending on the cell population and perhaps the density of surface-associated CSF-1 receptor. We believe that expression of CSF-1 receptors plays an important role not only in the regulation of normal monocyte-macrophage cell growth as already described in the literature but also in leukemic cells where it provides the “target” for the corresponding factor to exert its differentiation action.