Expression level of DEK in chronic lymphocytic leukemia is regulated by fludarabine and Nutlin-3 depending on p53 status
Expression level of DEK in chronic lymphocytic leukemia is regulated by fludarabine and Nutlin-3 depending on p53 status
复制标题
慢性淋巴细胞白血病中 DEK 的表达水平受氟达拉滨和 Nutlin-3 的调节，具体取决于 p53 状态
DOI：
10.4161/cbt.22252
复制
发表时间：
2012-12-01
影响因子：
3.6
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Wang, Dong-Mei;Liu, Ling;Xu, Wei
人类致癌基因 DEK 已被证明在多种肿瘤中表达上调。本研究的目的是调查慢性淋巴细胞白血病 (CLL) 中的 DEK 表达水平，分析 DEK 表达与 CLL 预后标志物之间的相关性，并表征 DEK 在化疗药物或 p53 途径非基因毒性激活剂反应中的作用。通过实时定量逆转录酶聚合酶链式反应 (qPCR) 评估 DEK mRNA，并在体外用氟达拉滨或 Nutlin-3 处理原发性 CLL 样本，以探索 p53 状态与 DEK mRNA 表达的相互作用。 65 名 CLL 患者中 DEK mRNA 的中位表达水平为 6.792 × 10−2 (1.438 × 10−2−3.201 × 10−1)。在免疫球蛋白重链可变 (IGHV) 基因未突变 (p = 0.025)、CD38 阳性 (p = 0.047)、del(17p13) (p = 0.006) 的 CLL 患者中观察到 DEK mRNA 表达显着增加。在 p53 功能正常或没有 p53 缺失或突变的原代 CLL 细胞中，氟达拉滨和 Nutlin-3 均显着下调 DEK（p = 0.042，p = 0.038；p = 0.021，p = 0.017；p = 0.037，p = 0.017）。然而，在p53功能障碍或p53缺失或突变的原代CLL细胞中未观察到DEK下调（p = 0.834，p = 0.477；p = 0.111，p = 0.378；p = 0.263，p = 0.378）。这些数据表明DEK可能用于评估CLL患者的预后，氟达拉滨和Nutlin-3根据p53状态调节DEK表达。
Human oncogene DEK has been shown to be upregulated in a number of neoplasms. The purpose of this study was to investigate DEK expression level in chronic lymphocytic leukemia (CLL), analyze the correlation between DEK expression and CLL prognostic markers, and characterize the role of DEK in the response to either chemotherapeutic drugs or nongenotoxic activators of the p53 pathway. DEK mRNA was evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR), and primary CLL samples were treated in vitro with either fludarabine or Nutlin-3 to explore the interaction of p53 status and DEK mRNA expression. The median expression levels of DEK mRNA were 6.792 × 10−2 (1.438 × 10−2−3.201 × 10−1) in 65 patients with CLL. A marked increase of DEK mRNA expression was observed in the CLL patients with unmutated immunoglobulin heavy chain variable (IGHV) gene (p = 0.025), CD38-positive (p = 0.047), del(17p13) (p = 0.006). Both fludarabine and Nutlin-3 significantly downregulated DEK in the primary CLL cells which were with normal function of p53, or without deletion or mutation of p53 (p = 0.042, p = 0.038; p = 0.021, p = 0.017; p = 0.037, p = 0.017). However, the downregulation of DEK was not observed in the primary CLL cells which were with dysfunction of p53, or with deletion or mutation of p53 (p = 0.834, p = 0.477; p = 0.111, p = 0.378; p = 0.263, p = 0.378). These data show that DEK might be applied for the assessment of prognosis in patients with CLL, and fludarabine and Nutlin-3 regulate DEK expression depended on p53 status.