CSN复合物在ATRA诱导APL细胞分化过程中的表达及其意义

Expression of CSN Complex in ATRA-induced APL Cell Differentiation and Its Clinical Significance

目的:探索CSN复合物在急性早幼粒细胞白血病(APL)患者中的表达及其在全反式维甲酸(ATRA)诱导急性早幼粒细胞分化中的作用。方法:以NB4细胞为实验对象,通过细胞形态学观察及流式细胞术的CD11b检测以监测ATRA诱导分化;用Western blot及逆转录荧光定量PCR检测CSN复合物在细胞分化过程中的变化,并采用实时荧光定量PCR的方法检测APL患者及其治疗缓解后CSN复合物亚基的表达情况。结果:在NB4细胞中ATRA可诱导细胞CD11b表达,细胞在形态上呈明显分化特征;CSN复合物各个亚基的表达水平随细胞分化逐渐下调。APL患者中CSN表达水平明显高于非白血病患者组(P<0.05),ATRA诱导缓解治疗后达完全缓解的患者中CSN的表达水平较治疗前明显下降。结论:CSN复合物在APL中高表达,ATRA可以下调CSN复合物的表达,提示CSN复合物在APL发病和治疗中发挥着重要作用。

Objective : To investigate the expression of CSN complex( COP9 signalsome subunits) in the patients with acute promyelocytic leukemia( APL) and its significance in the ATRA-induced APL differentiation. Methods:Using the NB4 cells as a model,morphologic observation and myeloid differentiation marker CD11 b detection were used to monitor ATRA-induced APL differentiation,the expression of CSN complex in cell differentiation was detected by Western blot and reverse transcription real time fluorescent quantitative PCR( RT-qPCR) method. RT-qPCR was also used to detect the relative expression level of COP9 signalosome subunits in the APL patients and remission after treatment. Results: ATRA could obviously enhance CD11 b expression; the cell morphology showed obvious differentiation characteristics. During the differentiation,the expression of COP9 signalosome subunits was downregulated by ATRA. Meanwhile,the CSN expression level in newly diagnosed APL patients was much higher than that in controls( non-leukemia)( P < 0. 05). The level of CSN expression was obviously down-regulated when APL patients achieved complete remission. Conclusion: The high CSN expression level in APL patients can be down-regulated by ATRA. CSN complex may have a significant effect on the pathogenesis and therapy of APL.