Breitman T R, Gallo R C
Blood Cells. 1981;7(1):79-89.
The Hl-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly 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 dimethylsulfoxide and hexamethylene bisacetamide. However, these compounds are either nonphysiological or induce HL-60 at concentrations that are markedly greater than physiological. We have now found that retinoic acid is the most potent inducer of granulocytic differentiation of HL-60. This compound induces differentiation at concentrations 1/10(3) to 1/10(6) the concentration of other inducers and at concentrations that are physiological. These findings prompted an investigation of the sensitivity to retinoic acid of fresh human myelocytic leukemia cells in primary suspension culture. Of 21 leukemic specimens, only cells from the 2 patients with acute promyelocytic leukemia differentiated in response to retinoic acid. Thus, as with HL-60, it appears that retinoic acid specifically induces granulocytic differentiation of leukemic promyelocytes and may have therapeutic utility in the treatment of acute promyelocytic leukemia. In addition, our results suggest that retinoic acid 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。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。然而，这些化合物要么是非生理性的，要么在显著高于生理浓度的情况下诱导HL-60细胞分化。我们现已发现，视黄酸是HL-60细胞粒细胞分化的最有效诱导剂。该化合物诱导分化的浓度是其他诱导剂浓度的1/10³至1/10⁶，且处于生理浓度。这些发现促使我们对原代悬浮培养的新鲜人髓细胞白血病细胞对视黄酸的敏感性进行研究。在21份白血病标本中，只有来自2例急性早幼粒细胞白血病患者的细胞对视黄酸有反应并发生分化。因此，与HL-60细胞一样，视黄酸似乎特异性地诱导白血病早幼粒细胞的粒细胞分化，可能在急性早幼粒细胞白血病的治疗中具有治疗作用。此外，我们的结果表明视黄酸可能也参与某些造血细胞的分化。
