通过微阵列技术检测Dlk1基因在骨髓增生异常综合征中的表达及其对白血病细胞的影响。

Expression of Dlk1 gene in myelodysplastic syndrome determined by microarray, and its effects on leukemia cells.

作者信息

Qi Xiaofei, Chen Zixing, Liu Dandan, Cen Jiannong, Gu Ming

机构信息

Leukemia Research Division, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, First Affiliated Hospital, Soochow University, Suzhou, PR China.

出版信息

Int J Mol Med. 2008 Jul;22(1):61-8.

PMID:18575777

Abstract

Delta-like-1 (Dlk1, also Pref-1), a transmembrane and secreted protein, is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We found that the expression of Dlk1 was up-regulated in CD34+ cells from patients with myelodysplastic syndrome (MDS) by analyzing the gene expression profiles determined by microarray. The expression levels of Dlk1 mRNA frequently observed higher in the bone marrow mononuclear cells of MDS patients was confirmed by real-time RT-PCR. Forced expression of Dlk1 in transfected K562 cells enhanced proliferation, affected apoptosis induced by As2O3, and also influenced cell cycle induced by 12-O-tetra decanoylphorbol-acetate (TPA). By using the same experimental system we found that forced expression of Dlk1 increased the mRNA levels of HES1. It also inhibited p38 phosphorylation in transfected K562 cells treated with TPA. These results warrant further investigation of the role of Dlk1 in abnormal hematopoiesis in MDS.

摘要

Delta样蛋白1（Dlk1，也称为Pref-1）是一种跨膜分泌蛋白，属于表皮生长因子样家族成员，与Notch/Delta/Serrate同源。通过分析微阵列测定的基因表达谱，我们发现骨髓增生异常综合征（MDS）患者的CD34+细胞中Dlk1的表达上调。实时RT-PCR证实，MDS患者骨髓单个核细胞中Dlk1 mRNA的表达水平经常较高。在转染的K562细胞中强制表达Dlk1可增强增殖，影响三氧化二砷诱导的细胞凋亡，还可影响十四酰佛波醇乙酯（TPA）诱导的细胞周期。通过使用相同的实验系统，我们发现强制表达Dlk1可增加HES1的mRNA水平。它还抑制了用TPA处理的转染K562细胞中p38的磷酸化。这些结果值得进一步研究Dlk1在MDS异常造血中的作用。