Induction of colony-stimulating factor response in myeloid leukaemia cell lines

Untreated, late passage HL60 promyelocytic and KG1 myeloblastic leukaemia cells did not increase proliferation with placenta or Mo T cell conditioned medium containing colony-stimulating factor (CSF) nor with partially purified, recombinant granulocyte/macrophage (GM)-CSF. However, after induction with DMSO or 1,25-dihydroxy-vitamin D3, HL60 cells showed dose-dependent increases in proliferation with crude and purified CSFs. CSF responses and macrophage differentiation were induced in KG1 cells by treatment with tetradecanoylphorbol-acetate (TPA). When cells were exposed to inducing agents for varying periods, washed and exposed to CSF, proliferative responses were related to time of exposure. Cells exposed for 1-4 d showed post-induction CSF-induced proliferation, but cells induced for 5-6 d were inhibited by CSF. Induction of CSF response appeared linked to differentiation, since KG1 cells differentiated with TPA and developed CSF-induced proliferative responses, but showed no differentiation or CSF induced proliferation after treatment with vitamin D3. When HL60 cells were continuously exposed to DMSO or vitamin D3, overall cell production was increased by placenta conditioned medium, but cultures still became senescent and died after several weeks. Cells continuously cultured with DMSO were predominantly macrophages, indicating lineages of DMSO-induced differentiation were modified by continuous culture or the presence of CSF. After treatment with chemical inducers, proliferation of myeloid leukaemia lines is stimulated by CSF, providing a model for post-deterministic regulation of normal and malignant myeloid cell production.