转录因子LYL1在白血病患者中的表达及作用研究  

Expression of transcription factor LYL1 in leukemia and its possible role in leukemogenesis

作　　者：孟月生[1] 张燕香[1] 艾工文[1] 孟秀琴[1] 刘葳[1] 魏蓉[1] 蒋卫[1] 

机构地区：[1]同济大学上海第十人民医院血液科,上海200072

出　　处：《中华血液学杂志》2008年第11期749-752,共4页Chinese Journal of Hematology

基　　金：基金项目：上海市浦江人才计划（07PJ14088）

摘　　要：目的探讨转录因子LYL1在不同白血病患者中的表达及在白血病发病中的作用。方法应用荧光实时定量聚合酶链反应检测LYL1在不同类型白血病患者中的表达情况；应用特异性小干扰（si）RNA抑制LYL1的表达，观察LYL1表达下调对于白血病细胞系K562细胞增殖和分化能力的影响。结果与正常骨髓CD34^＋细胞相比，LYL1在多数急性髓系白血病（AML）（急性早幼粒细胞白血病除外）和急性淋巴细胞白血病（ALL）患者中都有异常高表达，AML完全缓解患者表达水平（1．400）较AML未缓解患者（9．985）明显下降（P〈0．01）；部分慢性粒细胞白血病（CML）患者的检测结果显示LYL1在CML急变期的表达（7．831）高于慢性期（1．672）（P〈0．01）。联合使用三种特异性siRNA可使K562细胞LYL1表达水平明显下调且对细胞生长和集落形成能力有一定抑制作用。结论在AML、ALL患者中均有LYL1异常表达。通过siRNA干扰抑制特定癌基因表达对于抑制白血病细胞的增殖有一定效果，在治疗恶性血液病方面具有临床应用潜力。Objective To study the expression of transcription factor LYL1 in leukemia and its possible role in leukemogenesis. Methods Fluorescence real time quantitative polymerase chain reaction was used to detect the expression levels of LYL1 in leukemias. Specific siRNA was used to silence the expression of LYL1 in K562 cells. Results Compared to CD34 positive cells from normal bone marrow, the expression of LYL1 was significantly elevated in patients with acute myeloid leukemia （AML） and acute lymphoblastic leukemia （ALL）. LYL1 expression was higher in chronic myeloid leukemia （CML） in blastie crisis than that in chronic phase（7. 831 vs 1. 672, P 〈 0.01 ）. LYL1 expression in AML in complete remission （CR） was down-regulated as compared with that of un-remission patients（ 1. 400 vs 9. 985, P 〈 0.01 ）. Down-regulation of endogenous expression of LYL1 in K562 cells by a combination of three specific siRNA could inhibit cellular growth and clonogenecity to some extent. Conclusion Over-expression of LYL1 is highly associated with AML as well as ALL. RNA interference targeting specific oncogenes such as LYL1 is potentially useful in the treatment of hematological malignancies.

关 键 词：基因 LYL1 基因表达 白血病 RNA干扰 

分 类 号：R686[医药卫生—骨科学]