Wang S Y, Liu S T, Wang S J, Ho C K
Department of Medical Research, Veterans General Hospital, Taipei, Taiwan, Republic of China.
Leuk Res. 1989;13(12):1091-7. doi: 10.1016/0145-2126(89)90154-9.
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.
使用不同浓度的视黄酸（RA，10⁻⁹至10⁻⁷M）、淋巴细胞衍生的分化诱导因子（DIF，10 - 30%）、重组人粒细胞集落刺激因子（rG - CSF，100 - 4000 U/ml）和粒细胞 - 巨噬细胞集落刺激因子（rGM - CSF，100 - 4000 U/ml）诱导HL - 60早幼粒细胞白血病细胞分化。浓度为10⁻⁷M的视黄酸在悬浮培养和软琼脂培养中均能显著抑制HL - 60细胞的生长，并诱导这些细胞分化为能够还原硝基蓝四氮唑并摄取乳胶珠的成熟粒细胞。30%（v/v）的DIF也是HL - 60细胞分化的有效诱导剂，但它促使细胞成熟为单核细胞而非粒细胞。相比之下，在所有测试浓度下，rG - CSF和rGM - CSF在悬浮培养或琼脂培养中对HL - 60细胞均无生长抑制作用，这些因子也不能诱导HL - 60细胞获得更成熟的粒细胞或单核细胞表型。此外，将rG - CSF/rGM - CSF添加到含视黄酸的HL - 60培养物中时，没有分化增强作用。这些结果表明，基于诱导分化的原理使用集落刺激因子治疗髓细胞白血病是无效的。
