Bianchi N, Osti F, Rutigliano C, Corradini F G, Borsetti E, Tomassetti M, Mischiati C, Feriotto G, Gambari R
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Br J Haematol. 1999 Feb;104(2):258-65. doi: 10.1046/j.1365-2141.1999.01173.x.
The human leukaemic K562 cell line can be induced in vitro to undergo erythroid differentiation by a variety of chemical compounds, including haemin, butyric acid, 5-azacytidine and cytosine arabinoside. Differentiation of K562 cells is associated with an increased expression of embryo-fetal globin genes, such as the zeta, epsilon and gamma globin genes. Therefore the K562 cell line has been proposed as a useful in vitro model system to determine the therapeutic potential of new differentiating compounds as well as to study the molecular mechanism(s) regulating changes in the expression of embryonic and fetal human globin genes. Inducers of erythroid differentiation which stimulate gamma-globin synthesis could be considered for possible use in the experimental therapy of those haematological diseases associated with a failure in the expression of adult beta-globin genes. In this paper we demonstrated that the G + C selective DNA-binding drugs chromomycin and mithramycin were powerful inducers of erythroid differentiation of K562 cells. Erythroid differentiation was associated with an increase in the accumulation of (a) Hb Gower 1 and Hb Portland and (b) gamma-globin mRNA.
人白血病K562细胞系可在体外被多种化合物诱导进行红系分化,这些化合物包括血红素、丁酸、5-氮杂胞苷和阿糖胞苷。K562细胞的分化与胚胎-胎儿珠蛋白基因(如ζ、ε和γ珠蛋白基因)表达增加有关。因此,K562细胞系被认为是一种有用的体外模型系统,可用于确定新的分化化合物的治疗潜力,以及研究调节胚胎和胎儿人珠蛋白基因表达变化的分子机制。刺激γ珠蛋白合成的红系分化诱导剂可考虑用于与成人β珠蛋白基因表达失败相关的血液疾病的实验治疗。在本文中,我们证明了G + C选择性DNA结合药物放线菌素和光神霉素是K562细胞红系分化的强力诱导剂。红系分化与以下情况的积累增加有关:(a)Hb Gower 1和Hb Portland;(b)γ珠蛋白mRNA。