白血病细胞中端粒酶抑制因子Pinx1的表达与端粒酶活性关系的研究

Expression of telomerase inhibitor Pinx1 in leukemia cells and its correlation with telomerase activity

目的:研究端粒酶抑制因子Pinx1在急性白血病细胞中的表达和在急性早幼粒白血病细胞株细胞NB4分化过程中的表达改变,分析其表达与端粒酶逆转录酶hTERT表达的关系,以了解白血病细胞中Pinx1对端粒酶的作用及可能机制。方法:荧光定量RT-PCR检测30例急性白血病细胞中Pinx1与hTERTmRNA的表达,进一步在ATRA诱导的急性早幼粒白血病细胞株细胞NB4分化过程中检测Pinx1及hTERTmRNA表达,分析两者之间的相关性。结果:Pinx1在急性白血病细胞中的表达(0·00312,5·42×10-4-0·024)明显高于正常人骨髓单个核细胞(7·89×10-4,0-0·00863,P<0·01),与hTERT的表达呈正相关(r=0·296,P<0·05)。Pinx1表达随NB4细胞分化逐渐下降,与hTERT呈正相关(r=0·900,P<0·05)。结论:Pinx1虽然为端粒酶活性的抑制因子,但在白血病细胞中与端粒酶活性的调控方向一致,提示Pinx1的表达改变可能是继发于hTERT的一种负反馈反应,目的是保持端粒酶活性的稳定,具体机制尚待进一步研究。

AIM： To study the expression of telomerase inhibitor Pinxl in acute leukemia cells and during the differentiation of acute promyelocytic leukemia cells, and to realize its effect on telomerase activity. METHODS ： Realtime quantitative PCR with fluorescence probe hybridization was used to measure the expression of Pinxl and hTERT mRNA in acute leukemia cells and during differentiation of NB4 cells induced by ATRA. The correlations between Pinxl and hTERT expression were also analyzed. RESULTS： Pinxl mRNA expression in acute leukemia samples （0. 00312, 5.42 × 10^-4 - 0. 024） was significantly higher than that in normal bone marrow mononuclear cells （7.89 × 10^-4, 0 -0. 00863, P 〈 0. 01 ）. The expression of Pinxl mRNA had significant positive correlation with hTERT mRNA expression （ r = 0. 296, P 〈 0.05 ）. Pinxl mRNA expression decreased during differentiation, its expression was positive correlated with hTERT mRNA expression （ r = 0. 900, P 〈 0. 05 ）. CONCLUSIONS ： As an inhibitor of telomerase, however, Pinxl also had the same direction of regulation with telomerase activity in acute leukemia cells, suggesting its expression variation may be a subsequent reaction induced by that of hTERT to stabilize telomerase activity. The exact mechanisms remained to be verified.