慢性粒细胞白血病细胞eIF4E mRNA表达及影响因素

mRNA expression of eIF4E gene and its influencing factor in CML cells

目的:初步探索真核细胞翻译起始因子4E(eIF4E)在慢性粒细胞白血病(CML)不同病程,包括慢性期(CP)、加速期(AP)、急变期(BC)、急变治疗后(BC-R)骨髓细胞中mRNA表达及其在K562细胞中的表达影响因素.方法:RT-PCR检测25例骨髓样本[CML急变期(CML-BC)10例,慢性期(CML-CP)8例,加速期(CML-AP)1例,急变期治疗后(CML-BC-R)3例,贫血对照3例]eIF4E mRNA表达,及其中9例CML eIF4E和RNA结合蛋白K(hnRNP K)mRNA表达,并分析两种基因表达相关性.用酪氨酸激酶抑制剂STI571处理K562细胞,并用hnRNP K短发夹RNA(shRNA)逆转录病毒载体感染K562细胞,经G418稳定筛选,分别检测eIF4E mR-NA表达变化.结果:与贫血对照组相比,CML-BC和CML-BC-R eIF4E mRNA表达差异有统计学意义(P<0.05),而与CML-CP无统计学意义,hnRNP K与eIF4E mRNA表达呈线性相关(r=0.79,P<0.01).STI571能轻微下调K562细胞eIF4E mRNA表达.hnRNP K干扰组hnRNP K和eIF4E mRNA表达比空载对照组分别下降55.22%,55.27%.结论:CML急变期eIF4E mRNA表达显著增高,BCR/ABL融合蛋白可能参与调节eIF4E mRNA表达但效应有限,hnRNP K分子在eIF4E mRNA表达调控中可能发挥一定作用.

AIM： To explore mRNA expression of the eukaryotic translation initiation factor-4E （ cIF4E ） in Chronic Myelogenous Leukemia（CML） bone marrow （BM） cells at different stages of the disease including chronic phase （CP）, accelerated phase （ AP）, blast crisis （ BC ）, blast crisis with treatment （ BC-R ）, and the influencing factors of eIF4E mRNA expression in K562 cells. METHODS： RT-PCR was taken to analyze eIF4E mRNA in 25 BM samples（8 CML-CP, 1 CML-AP, 10 CML-BC, 3 CML- BC-R, 3 anemia control）and hnRNP K mRNA in 9 CML patients followed by the analysis of its correlation with eIF4E mRNA, and eIF4E mRNA expression in K562 cells after STI571 treatment, and K562 cells with G418 stable screening after heterogeneous nuclear ribonucleoprotein K （ hnRNP K） short hairpin RNA （ shRNA） retrovirus infection respectively. RESULTS： eIF4E mRNA in CML-BC （P 〈 0.05 ） or CML-BC-R group （ P 〈 0.05 ） but not CML-CP group（ P 〉 0.05 ） was significantly higher than that in the control group. There was linear correlation between mRNA expression of hnRNP K and eIF4E gene （ r = 0.79, P 〈 0.01 ）. STI571 treatment slightly down-regulated eIF4E mRNA expression. eIF4E and hnRNP K mRNA decreased by about 55.27% and 55.22% respectively in K562 cells expressing hnRNP K shRNA. CONCLUSION： eIF4E mRNA is significantly higher in CML-BC, in which BCR/ABL might paticipate, but not very powerfully, hnRNP K probably plays a role in the regulation of eIF4E mRNA expression.