目的:慢性粒细胞白血病(chronic myeloid leukemia,CML)急变中伴随着多聚胞嘧啶结合蛋白E2[poly(rC)-binding protein E2,hnRNP E2]的表达异常。本研究初步探讨hnRNP E2诱骗RNA对DP210细胞在动物体内致白血病的作用。方法:分别将稳定表达hnRNP E2诱骗RNA野生序列的DP210-pGD细胞、表达突变序列的DP210-pGM细胞以及对照组DP210细胞通过尾静脉注射CH3小鼠,观察各组小鼠的一般情况以及生存期;外周血白细胞计数(white blood count,WBC)并行外周血涂片及骨髓涂片检查;观察各组小鼠肝、脾和肺组织病理组织学变化。结果:各组小鼠注射不同细胞20 d后,DP210-pGD组小鼠毛色依然发亮,活动力和生长状况较良好,WBC为(8.36±2.81)×109/L,外周血涂片中仅见少量白血病细胞;DP210和DP210-pGM组小鼠的WBC分别为(40.52±12.89)×109/L和(38.73±8.26)×109/L(P〈0.01),外周血涂片均可见较多的幼稚白血病细胞。与DP210组和DP210-pGM组小鼠相比,DP210-pGD组小鼠骨髓增生不明显,仍可见许多成熟的粒细胞,肝、脾和肺组织的病理学结构改变较少,白血病细胞浸润程度较低,且生存期明显延长(P〈0.01),但最终66 d时全部死亡。结论:hnRNP E2诱骗RNA能延缓DP210细胞对小鼠的致瘤能力。
Objective:The blast crisis phase of chronic myeloid leukemia(CML) is accompanied with abnormal expression of heterogeneous poly(rC)-binding protein E2(hnRNP E2).The present study is to investigate the effect of decoy RNA of hnRNP E2 on the tumorigenic ability of 32D-BCR/ABL(DP210) cells in inducing leukemia in vivo.Methods:The control DP210 cells,DP210-pGD cells that stably expressed wild type of decoy RNA of hnRNP E2 and DP210-pGM cells that stably expressed the mutant-type of decoy RNA of hnRNP E2 were injected into the tail vein of CH3 mice,respectively.The general situation and survival time of mice in each group were observed.The number of peripheral white blood cells was counted.The blood and bone marrow smears were examined.The pathological changes of the liver,spleen,and lung were observed.Results:At 20 d after injection,the hair of DP210-pGD mice were still shiny.These mice were in an active,and a more favorable growth condition with WBC count(8.36±2.81)×109/L,and a small amount of leukemia cells in peripheral blood smear.While the WBC of DP210 and DP210-pGM mice were(40.52±12.89) × 109/ L and(38.73±8.26) × 109/ L(P 0.01),respectively.A lot of immature leukemia cells were observed in peripheral blood smears.Compared with DP210 and DP210-pGM mice,the hyperplasia of bone marrow cells in DP210-pGD mice was not obvious and a number of mature granulocytes could be seen.The histological structures of the liver,spleen,and lung changed less,the degree of infiltration of leukemic cells was lower and the survival time was significantly prolonged(P0.01).But all the mice eventually died in 66 d.Conclusion:hnRNP E2 decoy RNA delayed tumorigenesis of 32D-BCR/ABL cells in mice.