Establishment and characterization of a unique human cell line that proliferates dependently on GM‐CSF, IL‐3, or erythropoietin

Abstract

We have established a novel cell line, designated as TF‐1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or on interleukin‐3 (IL‐3) and carried a homogeneous chromosomal abnormality (54X). Erythropoietin (EPO) also sustained the short‐term growth of TF‐1, but did not induce erythroid differentiation. These three hematopoietic growth factors acted on TF‐1 synergistically. Transforming growth factorβ and interferons inhibited the factor‐dependent growth of TF‐1 cells in a dose‐dependent fashion, and monocyte‐colony stimulating factor and interkeukin‐1 enhanced the GM‐CSF‐dependent growth of TF‐1. Ultrastructural studies revealed some very immature features in this cell line. Although TF‐1 cells do not express glycophorin A or carbonyl anhydrase I, the morphological and cytochemical features, and the constitutive expression of globin genes, indicate the commitment of TF‐1 to erythroid lineage. When induced to differentiate, TF‐1 entered two different pathways. Specifically, hemin and delta‐arninolevulinic acid induced hemoglobin synthesis, whereas TPA induced dramatic differentiation of TF‐1 into macrophage‐like cells. In summary, TF‐1 is a cell lineof immature erythroid origin that requires GM‐CSF, IL‐3, or EPO for its growth and that has the ability to undergo differentiation into either more mature erythroid cells or into macrophage‐like cells. TF‐1 is auseful tool for analyzing the human receptors for IL‐3, GM‐CSF, and EPO or the signal transduction of these hemopoietic growth factors.