Comparison of the effects of all-trans and cis-retinoic acid on the blast stem cells of acute myeloblastic leukemia in culture.
Comparison of the effects of all-trans and cis-retinoic acid on the blast stem cells of acute myeloblastic leukemia in culture.
复制标题
全反式和顺式视黄酸对培养的急性髓细胞白血病母细胞干细胞的影响比较。
作者：
S. Tohda;J. Curtis;E. McCulloch;M. Minden
最近的研究表明，急性早幼粒细胞白血病（APL）细胞具有特征性易位，涉及17号染色体上的视黄酸受体和15号染色体上的myl蛋白。APL患者对全反式维甲酸治疗有反应。最近报道了具有t15;17（NB 4）的细胞系;该细胞系对全反式维甲酸有分化反应。最近也有报道表明，在新鲜获得的APL细胞中，全反式视黄酸比顺式视黄酸在诱导分化方面更有活性。比较全反式视黄酸和顺式视黄酸对新鲜获得的AML细胞、不含t15;17的细胞系和NB 4细胞的培养物中生长的影响。虽然所有这些AML群体对两种形式的视黄酸都有反应，但与顺式视黄酸相比，NB 4细胞仅对全反式视黄酸更敏感。当NB 4细胞暴露于悬浮液中时观察到差异，而当将甲基纤维素中的集落形成用作终点时则没有。这两种形式的维甲酸增加了原始细胞对阿糖胞苷的敏感性;对于NB 4细胞，当使用全反式维甲酸而不是顺式维甲酸时，致敏性要大得多。我们的结论是，全反式维甲酸的增加的影响是特定的APL细胞，维甲酸的主要影响是对原始干细胞的自我更新。
Recent work has shown that acute promyelocytic leukemia (APL) cells have a characteristic translocation involving the retinoic acid receptor on chromosome 17 and the myl protein on chromosome 15. Patients with APL respond to the administration of all-trans-retinoic acid. A cell line with t15;17 (NB4) has recently been reported; this line responds to all-trans-retinoic acid with differentiation. There is also a recent report showing that all-trans-retinoic acid is more active than cis-retinoic acid in inducing differentiation in freshly obtained APL cells. All-trans-retinoic and cis-retinoic acid are compared for their effects on growth in culture of freshly obtained AML cells, cell lines without t15;17, and NB4 cells. While all of these AML populations responded to both forms of retinoic acid, NB4 cells only were much more sensitive to all-trans-retinoic acid compared to cis-retinoic acid. The difference was seen when the NB4 cells were exposed in suspension and not when colony-formation in methylcellulose was used as an end point. Both forms of retinoic acid increased the sensitivity of blast cells to cytosine arabinoside; for NB4 cells, the sensitization was much greater when all-trans-retinoic acid was used rather than cis-retinoic acid. We conclude that the increased effects of all-trans-retinoic acid are specific for APL cells, and that a major effect of retinoic acid is on blast stem cell self-renewal.