阿克拉霉素A、维甲酸对人原代白血病细胞体外诱导分化作用研究

【作者】 于非；

【导师】 张之南； 侯虞华；

【作者基本信息】 中国协和医科大学 ， 血液内科， 1989， 博士

【摘要】 本试验采用悬浮培养法研究了阿克拉霉素A、全反式维甲酸对人急性非淋巴细胞白血病原代细胞的体外诱导分化作用。培养一周，ACMA60nM组21例中有13例成熟细胞百分数此对照组提高20.0％以上。与对照组相此，13例病人活细胞数、幼稚细胞数降低非常显著（P＜0.01），成熟细胞数变化不明显。其中8例成熟细胞绝对值有所增加，5例减少。药物处理后的13例细胞NBT还原率、释放活性氧能力较对照组增强（P＜0.05），细胞膜C₃受体阳性率及硷性磷酸酶染色无明显改变。RA10^-6M组24例中有5例成熟细胞百分数此对照组提高20.0％以上。与对照组相比这5例病人活细胞数变化不明显而幼稚细胞数减少（P＜0.01）成熟细胞数增加显著（P＜0.05）。NBT还原率、释放活性氧能力及细胞膜C-3受体出现率均显著高于对照组（P＜0.05），硷磷酶变化不明显。 上述结果提示，小剂量ACMA体外可能对某些白血病细胞有诱导分化作用，但其使白血病细胞减少主要是细胞毒作用所致，ACMA诱导分化后的细胞氧化功能增强。RA体外可使早幼粒白血病细胞分化成熟，也可使极少数M2白血病细胞分化。经RA诱导成熟的细胞氧化能力及细胞膜C₃受体阳性率均明显提高。更多还原

【Abstract】 In this study,the differentiation-induction effects of Aclacinomycin-A and All-trans retinoic acid on fresh human ANLL cells in liquid suspension cultures were investigated. On the 7th day of cultivation,samples of 13 out of 21 patients in the flasks containing 60 nM of ACMA showed an increase of mature cells percentage>20.0% as compared with control flasks. In this 13 cases,the decreases of viable and immature cell counts were both significant（p<0.01）,but the increase of mature cell counts were not obvious. Eight of the 13 cases showed increase while 5 of the 13 cases showed decrease in mature cell counts.As compared with control,the percentage of NBT positive cells was higher（P<0.05）and the generation of reactive oxygen enhanced（P<0.05）in these 13 patients,but the percentages of cells with C₃ recepter and with alkaline phosphatase did not increase. Increase of percentage of mature cell（20.0% higher than control）was found in 5 from 24 cases treated with RA (10^-6M).Numbers of viable cell counts were not altered,while immature cell counts decreased（P<0.01） and mature cell counts increased as compared with control.In t his 5 cases, the percentage of NBT positive,C₃ receptor positive cells and the amount of generation of reactive oxygen were increased significantly （P<0.05）. The percentage of ALP positive cells did not change.The above results suggest that:in vitro,low dose ACMA in this study was able to induce differentiation of leukemia cells in some patients,but its main effect was suppression of leukemia cells due to cytotoxity.The oxidative function of induced mature cells increased.RA can induce differentiation not only in M₃ but in a few M₂ cases,The oxidative function and percentage of C₃ positive cell percentage increased significancly.更多还原