INDUCTION OF DIFFERENTIATION IN HL60 LEUKEMIC-CELLS - A CELL-CYCLE DEPENDENT ALL-OR-NONE EVENT

INDUCTION OF DIFFERENTIATION IN HL60 LEUKEMIC-CELLS - A CELL-CYCLE DEPENDENT ALL-OR-NONE EVENT
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DOI:
10.1016/0145-2126(84)90029-8
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发表时间:
1984-01-01
期刊:
影响因子:
2.7
通讯作者:
METCALF, D
METCALF, D
中科院分区:
医学3区
文献类型:
--
作者:
BOYD, AW;METCALF, D

文献摘要

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人白血病细胞系(HL 60)显示出有限的自发分化能力,但这种特性可以通过化学诱导剂大大增强。丁酸钠在4天的时间间隔内诱导几乎100%的HL 60细胞分化为具有多个单核细胞表型标志物的细胞。琼脂中的克隆形成分析表明,分化的细胞(自发或诱导)不可逆地失去了克隆形成的潜力。这似乎是一个全有或全无的过程,未受影响的细胞表现出未改变的克隆原性。集落形成动力学的研究表明,大多数(如果不是全部的话)细胞在丁酸盐存在下完成一次分裂,有时在丧失增殖潜力之前完成几次分裂。尽管加入丁酸盐时HL 60培养物中存在的细胞周期状态的统一谱,但所有分化的细胞均被阻滞在G1期。获得的证据表明,在细胞周期的一个限制阶段,无论是在周期的后期(G2-M)或早期G1的开关到分化途径发生。
The human leukemia cell line (HL60) shows a limited capacity to differentiate spontaneously, but this property can be greatly enhanced by chemical inducers. Sodium butyrate induced differentiation in virtually 100% of HL60 cells over a 4-day interval to cells with multiple phenotypic markers of monocytes. Clonogenetic analysis in agar demonstrated that differentiated cells (spontaneous or induced) irreversibly lost clonogenic potential. This appeared to be an all-or-none process with unaffected cells exhibiting unaltered clonogeneity. A study of the kinetics of colony formation showed that most, if not all, cells completed one division in the presence of butyrate and sometimes several divisions before loss of proliferative potential. Despite the uniform spectrum of cell cycle states present in HL60 cultures when butyrate was added, all differentiated cells were shown to be arrested in G1. Evidence was obtained suggesting that the switch into the differentiation pathway occurred during a restricted stage of the cell cycle, either late in the cycle (G2-M) or early in G1.