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.

Leukemia Research
S Y WangC K Ho

Abstract

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(-7) M 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.

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Citations

Mar 17, 1997·International Journal of Cancer. Journal International Du Cancer·S Y WangC K Ho
Mar 1, 1991·International Journal of Cell Cloning·D Metcalf
Jan 1, 1992·Progress in Growth Factor Research·P Van Vlasselaer
Jun 30, 1998·APMIS. Supplementum·J Olweus
Nov 21, 1992·Annals of the New York Academy of Sciences·S FerrariU Torelli

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