Breitman T R, Selonick S E, Collins S J
Proc Natl Acad Sci U S A. 1980 May;77(5):2936-40. doi: 10.1073/pnas.77.5.2936.
The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (greater than 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds, including butyrate and hypoxanthine and polar planar compounds such as dimethyl sulfoxide and hexamethylene bisacetamide. We have now found that retinoic acid (all-trans-retinoic acid) induces differentiation (as measured morphologically and by the ability to reduce nitroblue tetrazolium) of HL-60 at concentrations as low as 1 nM. Maximal differentiation (approximately 90%) occurs at 1 micro M, a concentration 1/500th to 1/160,000th the concentrations of butyrate (0.5 mM) and dimethyl sulfoxide (160 mM) that promote a similar increase in differentiation. Continuous exposure to retinoic acid is necessary for optimal differentiation, with the percentage of mature cells in the culture directly related to the length of time of exposure to retinoic acid. Retinoic acid and 13-cis-retinoic acid are equally effective in inducing differentiation of HL-60. Retinol (vitamin A), retinal, and retinyl acetate are approximately 1/1000th less potent. This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, a disease that has been looked upon as primarily involving a block in myeloid differentiation, and indicates that retinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.
HL-60细胞系源自一名急性早幼粒细胞白血病患者，在悬浮培养中持续增殖，主要由早幼粒细胞组成（超过90%）。这些细胞可通过与多种化合物共同孵育而被诱导分化为形态和功能上成熟的粒细胞，这些化合物包括丁酸盐、次黄嘌呤以及极性平面化合物，如二甲基亚砜和六甲撑双乙酰胺。我们现已发现，视黄酸（全反式视黄酸）在低至1 nM的浓度下即可诱导HL-60细胞分化（通过形态学测量以及还原硝基蓝四唑的能力来衡量）。最大分化率（约90%）出现在1 μM时，该浓度是促进类似分化增加的丁酸盐（0.5 mM）和二甲基亚砜（160 mM）浓度的1/500至1/160000。持续暴露于视黄酸对于最佳分化是必要的，培养物中成熟细胞的百分比与暴露于视黄酸的时间长度直接相关。视黄酸和13-顺式视黄酸在诱导HL-60细胞分化方面同样有效。视黄醇（维生素A）、视黄醛和醋酸视黄酯的效力约低1/1000。这项研究表明，类视黄醇可为急性髓性白血病的治疗提供一种治疗工具，急性髓性白血病一直被视为主要涉及髓系分化受阻的疾病，并表明类视黄醇除了其在上皮细胞分化中已明确的作用外，可能还参与某些造血细胞的分化。
