Potential pre‐screening for therapeutic agents that induce differentiation in human myeloid leukemia cells

Potential pre‐screening for therapeutic agents that induce differentiation in human myeloid leukemia cells
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诱导人髓系白血病细胞分化的治疗药物的潜在预筛选

DOI:
10.1002/ijc.2910250503
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发表时间:
1980
影响因子:
6.4
通讯作者:
L. Sachs
L. Sachs
中科院分区:
医学1区
文献类型:
--
作者:
Joseph Lothm;L. Sachs

文献摘要

被引文献

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已使用人类骨髓白血病细胞培养系来测试化疗中使用的化合物诱导这些白血病细胞部分或完全分化的能力。这些化合物诱导特定分化相关特性的能力不同。诱导 Fc 和 C3 玫瑰花结的有效性顺序为放线菌素-D > 胞嘧啶阿糖苷 > 丝裂霉素-C > 阿霉素 > 溴脱氧尿苷 > 羟基脲。放线菌素-D 诱导玫瑰花结所需的浓度比羟基脲诱导低 8212 倍。除溴脱氧尿苷外,所有这些化合物均诱导溶菌酶的合成和分泌,其效果与玫瑰花结相同,但只有放线菌素-D 和较小程度的溴脱氧尿苷诱导成熟粒细胞的形成。长春新碱仅诱导溶菌酶少量增加。结果表明,放线菌素-D 是这些人骨髓白血病细胞中最有效的分化诱导剂。有人建议,对个体患者进行预筛选,寻找能够诱导培养物中骨髓白血病细胞分化的最有效化合物,可能有利于基于诱导白血病细胞正常分化的化疗方案的治疗。
A cultured line of human myeloid leukemic cells has been used, to test for the ability of compounds used in chemotherapy to induce partial or complete differentiation of these leukemic cells. The compounds differed in their ability to induce specific differentiation‐associated properties. Effectiveness of induction of Fc and C3 rosettes was of the order actinomycin‐D > cytosine arabinoside > mitomycin‐C > adriamycin > bromodeoxyuridine > hydroxyurea. Induction of rosettes by actinomycin‐D required a 8212‐fold lower concentration than induction by hydroxyurea. All these compounds, except bromodeoxyuridine, induced the synthesis and secretion of lysozyme with the same order of effectiveness as for rosettes, but only actinomycin‐D and to a lesser extent bromodeoxyuridine induced the formation of mature granulocytes. Vincristine induced only a small increase in lysozyme. The results indicate that actinomycin‐D was the most potent inducer of differentiation in these human myeloid leukemic cells. It is suggested that pre‐screening of individual patients for the most effective compounds that can induce differentiation of their myeloid leukemic cells in culture, may prove beneficial for treatment in a from of chemotherapy based on the induction of normal differentiation in leukemic cells.