Ferrero D, Tarella C, Gallo E, Ruscetti F W, Breitman T R
Cancer Res. 1982 Nov;42(11):4421-6.
Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol ester-induced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-beta-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.
分析了二甲基亚砜诱导人早幼粒细胞白血病细胞系HL - 60分化对细胞复制的需求。通过硝基蓝四氮唑还原、吞噬作用和形态学标准判断，HL - 60细胞进行终末粒细胞分化的能力并未因细胞增殖的完全阻断而受损。在没有细胞生长的情况下，维甲酸、放线菌素D和丁酸也能诱导HL - 60细胞分化。这些结果以及早期证明佛波酯诱导HL - 60细胞巨噬细胞分化独立于DNA合成，表明在这些白血病细胞中增殖与成熟是分离的。在两种临床常用化疗药物（羟基脲和1 - β - D - 阿拉伯呋喃糖基胞嘧啶）的各种生长抑制浓度存在的情况下，维甲酸增强HL - 60细胞分化的能力并未改变。这些结果表明，旨在抑制白血病细胞增殖并诱导其分化的联合治疗方案可能是有益的。
