herg1基因调控慢性髓细胞白血病细胞的增殖和细胞周期

Regulation of cell proliferation and cell cycle in chronic myelogenous leukemia cells by herg1 gene

目的:研究herg1基因在慢性髓细胞白血病(CML)细胞的表达及其对CML细胞增殖和细胞周期的调控作用。方法:应用RT-PCR方法测定33例初治慢性髓细胞白血病患者和10例健康志愿者的骨髓细胞herg1基因的表达,检测特异性抑制剂处理后CML细胞株K562增殖凋亡和细胞周期的变化。结果:①在初发CML病例中,herg1mRNA的表达率是72.7%(24/33),高于正常对照(20%)(P<0.01)。CML加速期和急变期的herg1mRNA的表达率分别为75%和90.9%,高于正常对照(P<0.01),但是herg1的表达与CML的临床分期并无相关性(P>0.05)。②E-4031(1μmol/L)可呈时间依赖性抑制细胞增殖,不诱导明显凋亡。③E-4031阻滞K562细胞周期于G1期。结论:CML细胞herg1基因表达失调,IHERG抑制剂E-4031对K562细胞的增殖和细胞周期具有调控作用,herg1基因可能与CML发病机制相关。

Objective： To investigate the mRNA expression of hergl in chronic myeloid leukemia （CML） patients and to investigate the effects of IHERC; inhibitor E-4031 on the proliferation and apoptosis of human leukemia cell line （K562） . Method：The expression of myeloid cell hergl gene in 33 de novo CML patients and 10 normal control （NC） was detected by transcription polymerase chain reaction （RT-PCR）. The effects of E-4031 on the proliferation of K562 leukemia cells were assayed by MTT method, cell apoptosis and cell cycle by flow cytometry （FCM）. Result：①In the de novo CML cases, the expression rate of hergl mRNA was 72.7% （ 24/33 ）, which was higher than NC （20%） （P〈0.01）. The expression of hergl in CML-AP（90.9%） and CML-BC （75%） patients was higher than that in NC （P%0.01）, but no correlation between hergl expression and clinical staging of chronic myeloid leukemia （P〉0.05）. ②With E-4031 （1 μmol/ L） , the inhibitory of proliferation could be observed in a time-dependent manner without more apoptsis. ③E-4031 inhibited K562 cell cycle progression at the G1 phase. Conclusion： The overexpression of hergl gene has been confirmed for the first time in patients with chronic myeloid leukemia. IHERG inhibitor E-4031 inhibited the proliferation of CML cell line K562 partly via cell cycle arrest, hergl gene is related to the pathogenesis of CML.