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(-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.
Wang
S Y
SY
Department of Medical Research, Veterans General Hospital, Taipei, Taiwan, Republic of China.
Liu
S T
ST
Wang
S J
SJ
Ho
C K
CK
D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008214:Lymphocytes / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor