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

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hTERT mRNA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hTERT mRNA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。

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

AIM:To study the expression of telomerase inhibitor Pinx1 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 hybri dization was used to measure the expression of Pinx1 and hTERT mRNA in acute leu kemia cells and during differentiation of NB4 cells induced by ATRA.The correla tions between Pinx1 and hTERT expression were also analyzed. RESULTS:Pinx1 mRNA expression in acute leukemia samples (0.003 12,5.42×10-4-0.024) was significantly higher than that in normal bone marrow mononuclear cells (7.89×10-4,0-0.00863,P<0.01).The expre ssion of Pinx1 mRNA had significant positive correlation with hTERT mRNA express ion (r=0.296,P<0.05).Pinx1 mRNA expression decreased during differentiat ion,its expression was positive correlated with hTERT mRNA expression (r=0.9 00,P<0.05). CONCLUSIONS:As an inhibitor of telomerase,however,Pinx1 also h ad the same direction of regulation with telomerase activity in acute leukemia c ells,suggesting its expression variation may be a subsequent reaction induced b y that of hTERT to stabilize telomerase activity.The exact mechanisms remained to be verified.