INDUCTION OF DIFFERENTIATION OF THE HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE (HL-60) BY RETINOIC ACID
INDUCTION OF DIFFERENTIATION OF THE HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE (HL-60) BY RETINOIC ACID
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DOI：
10.1073/pnas.77.5.2936
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
COLLINS, SJ
中科院分区：
文献类型：
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作者：
BREITMAN, TR;SELONICK, SE;COLLINS, SJ
HL-60细胞系来源于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（约90%）。这些细胞可以通过多种化合物的培养诱导分化为形态和功能成熟的粒细胞。视黄酸（全反式视黄酸）在低至1 nM的浓度下诱导HL-60分化（通过形态学测量和通过还原硝基蓝四唑的能力）。最大分化（约90%）发生在1mu。M，丁酸盐（0.5 mM）和二甲基亚砜（160 mM）浓度的1/500至1/160,000，促进分化的类似增加。持续暴露于维甲酸是最佳分化的必要条件，培养中成熟细胞的百分比与暴露于维甲酸的时间长短直接相关。视黄酸和13-顺式视黄酸对HL-60的诱导分化效果相同。视黄醇（维生素A）、视网膜和视黄醇醋酸酯的效力约为千分之一。类维生素a可以为急性髓性白血病的治疗提供一种治疗工具，这种疾病被认为主要涉及髓细胞分化的阻断。类维生素a除了参与上皮细胞分化外，还可能参与某些造血细胞的分化。
The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (> 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds. 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 .mu.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. 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. In addition to their well-characterized involvement in epithelial cell differentiation, retinoids may also be involved in the differentiation of certain hematopoietic cells.