SELECTIVE BLOCK IN ERYTHROPOIETIN-INDUCED DIFFERENTIATION OF GROWTH FACTOR-INDEPENDENT RETROVIRALLY-INFECTED TF-1 CELLS

The erythroleukaemic cell line TF-1, infected with either the pBabe ne o retrovirus or the retrovirus bearing the human erythropoietin (hEpo) gene, developed three growth factor-independent clones. Erythropoieti n (Epo), interleukin-3 (IL-3) and granulocyte-macrophage colony stimul ating factor (GM-CSF) accelerated the proliferation of these clones. A utonomous growth of the clones was independent of Epo because it was n ot altered by Epo anti-sense oligonucleotides, nor was Epo detectable in culture supernatants. Cells from the mutant clones could not be ind uced by Epo to express glycophorin A and haemoglobin synthesis was mar kedly reduced. Haemin reversed the block in Epo-induced haemoglobin sy nthesis. Acquisition of growth factor-independence appears to be linke d with the selective loss of differentiation capacity. These cells may provide a useful model for the study of the mechanisms involved in le ukaemic transformation. (C) 1997 Elsevier Science Ltd.