原癌基因LMO2在白血病细胞的表达及对细胞增殖的影响

Expression of proto-oncogene LMO2 in leukemia cells and its impact on cellular proliferation

目的检测原癌基因LMO2在各种白血病中的表达情况,观察该基因表达量的改变对白血病细胞增殖的影响,探索LMO2在白血病发病中的作用。方法荧光实时定量聚合酶链反应;Western印迹实验;基因转染建立高表达LMO2的白血病细胞株;siRNA干扰技术;细胞克隆形成实验。结果LMO2基因在很多急性髓系和淋巴系白血病患者的表达水平高于慢性白血病患者及正常骨髓细胞,但LMO2转染的K562细胞克隆形成率下降,提示该基因在髓系白血病细胞的表达异常是一种伴随结果而不具有致癌作用。强表达LMO2的Molt-4细胞克隆形成率增加,应用特异siRNA可有效地下调其在Molt-4细胞的表达并使细胞克隆形成率下降,提示LMO2在T细胞白血病细胞中的表达有助于维持其增殖潜力。结论LMO2基因表达异常在T淋巴细胞中具有致癌作用,但在髓系细胞转化中可能只是一种伴随现象。

Objective To study the expression of proto-oncogene LMO2 in different leukemia cells and its effect on cellular proliferation in order to explore the role of proto-oncogene LMO2 in leukemogenesis. Methods Expressions of LMO2 in various types of leukemia cells were evaluated by using fluorescence quantitative real time polymerase chain reaction （RT-PCR）. Human erythroleukemia cell line K562 and T- cell leukemia line Molt-4 were transfected with LMO2 cDNA to create LMO2-overexpressing cells, Specific siRNA was used to target LMO2 in Molt-4 cells. Results Higher expression of LMO2 was detected in some of patients with acute myeloblastic leukemia （AML） or acute lymphoblastic leukemia （ALL）. However, enforced expression of LMO2 in K562 cells decreased cellular clonogenecity, suggesting the activation of the gene may not be important in the pathogenesis of myeloid leukemia. Nonetheless, transfection of LMO2 into Molt-4 cells increased plating efficiency. Useing of specific LMO2 siRNA was effective to down-regulate the endogenous expression of LMO2 in Molt-4 cells, and decreased cellular clonogenecity. Expression of LMO2 in T lymphocytes was helpful to keep its proliferation. Conclusion The aberrant expression of LMO2 may play a role in the transformation of T lymphocytes but is dispensable in myeloid leukemia.