Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents
Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents
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化学试剂诱导白血病细胞系分化后失去对正常骨髓集落形成的抑制
DOI：
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发表时间：
1985
期刊：
影响因子：
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通讯作者：
S. Robinson
中科院分区：
文献类型：
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作者：
H. Steinberg;A. Tsiftsoglou;S. Robinson
将人白血病细胞系 K562 和 HL-60 与正常骨髓 (BM) 细胞共培养。与 10(4) 个 K562 或 HL-60 细胞共培养可对正常 CFU-E 和 BFU-E 集落形成产生 50% 的抑制。然而，当相同数量的 K562 和 HL-60 细胞首先用诱导其分化的试剂处理两到五天时，观察到它们抑制 CFU-E 和 BFU-E 集落形成的能力逐渐丧失。 K562 细胞中的抑制物质是可溶的，存在于这些细胞培养物的条件培养基中。白血病细胞对 CFU-E 和 BFU-E 生长的抑制被逆转的程度与暴露于诱导剂的时间相关。预先使用诱导剂治疗五天后，抑制不再明显。事实上，在用 30 至 70 mumol/L 氯高铁血红素预处理五天的 K562 细胞共培养物中，观察到 CFU-E 生长的刺激高达 90%。用浓度低至30μmol/L的氯化血红素处理的K562细胞表现出血红蛋白合成增加并正常生长，但不再对CFU-E生长具有抑制作用。因此，正常 BM 生长抑制的逆转必定是由 K562 细胞的分化程度更高的状态引起的，而不是由治疗后这些细胞数量的减少引起的。因此，在培养的白血病细胞中诱导分化不仅改变恶性细胞表型，而且还允许改善伴随的正常骨髓祖细胞的生长。两者都是化疗的预期效果。
The human leukemic cell lines K562 and HL-60 were cocultured with normal bone marrow (BM) cells. Coculture with 10(4) K562 or HL-60 cells results in 50% inhibition of normal CFU-E and BFU-E colony formation. However, when the same number of K562 and HL-60 cells is first treated for two to five days with agents that induce their differentiation, a gradual loss in their capacity to inhibit CFU-E and BFU-E colony formation is observed. The inhibitory material in K562 cells is soluble and present in conditioned medium from cultures of these cells. The degree to which leukemic cell suppression of CFU-E and BFU-E growth is reversed is correlated with the time of exposure to the inducing agent. Suppression is no longer evident after five days of prior treatment with inducers. In fact, up to a 90% stimulation of CFU-E growth is observed in cocultures with K562 cells that have been pretreated with 30 to 70 mumol/L hemin for five days. K562 cells treated with concentrations of hemin as low as 30 mumol/L demonstrate increased hemoglobin synthesis and grow normally, but no longer have an inhibitory effect on CFU-E growth. Hence, reversal of normal BM growth inhibition must be caused by the more differentiated state of the K562 cells and not by a decrease in the number of these cells with treatment. Thus, induction of differentiation in cultured leukemic cells not only alters the malignant cell phenotype but also permits improved growth of accompanying normal marrow progenitor cells. Both are desired effects of chemotherapy.