Induction of differentiation in HL-60 cells by retinoic acid and lymphocyte-derived differentiation-inducing factor but not by recombinant G-CSF and GM-CSF

Various concentrations of retinoic acid (RA, 10^-9 to 10^-7 M), lymphocyte-derived differentiation-inducing factor (DIF, 10-30%), and recombinant human G-CSF (100-4000 U/ml) and GM-CSF (100-4000 U/ml) were used to induce the differentiation of the HL-60 promyelocytic leukemia cells. Retinoic acid at a concentration of 10^-7M could significantly inhibit the growth of HL-60 cells both in suspension and in soft agar cultures, and induced these cells to differentiate into mature granulocytes capable of reducing nitro-blue tetrazolium and ingesting latex beads. Thirty per cent (v/v) DIF was also an effective inducer of HL-60 cell differentiation, but it triggered the cells to mature into monocytes rather than granulocytes. In contrast, rG-CSF and rGM-CSF had no growth inhibitory effect on HL-60 cells either in suspension or in agar cultures at all concentrations tested, nor could these factors induce HL-60 cells to acquire the more mature granulocytic or monocytic phenotypes. Furthermore, rG-CSF/rGM-CSF had no differentiation-enhancing effect when added to RA-containing HL-60 cultures. These results argue against the efficacy of using CSFs for the treatment of myelocytic leukemia based on the principle of differentiation induction.