O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化和 MGMT 表达对霍奇金淋巴瘤细胞达卡巴嗪耐药性的影响。

Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine resistance of Hodgkin's lymphoma cells.

机构信息

Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany.

出版信息

Leuk Res. 2014 Jan;38(1):138-43. doi: 10.1016/j.leukres.2013.11.001. Epub 2013 Nov 13.

DOI:10.1016/j.leukres.2013.11.001

PMID:24284332

Abstract

We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter and mRNA expression in HL cells and assessed the response of these cells to dacarbazine. Expression of MGMT correlated with the presence of non-methylated promoters and cell lines with non-methylated promoters showed increased resistance against dacarbazine. KM-H2 cells expressed fusion transcripts between MGMT and proline-rich coiled-coil 2B (PRRC2B) but no wild type MGMT transcripts. Dacarbazine sensitivity suggested that fusion transcripts are translated into a protein with reduced functionality. MGMT promoter methylation predicts dacarbazine sensitivity of HL cells and it might be interesting to analyze this factor in HL patients.

摘要

我们分析了 HL 细胞中 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子的甲基化状态和 mRNA 表达，并评估了这些细胞对达卡巴嗪的反应。MGMT 的表达与非甲基化启动子的存在相关，并且具有非甲基化启动子的细胞系对达卡巴嗪表现出增加的抗性。KM-H2 细胞表达 MGMT 和富含脯氨酸的卷曲螺旋 2B（PRRC2B）之间的融合转录本，但没有野生型 MGMT 转录本。达卡巴嗪的敏感性表明融合转录本被翻译成一种功能降低的蛋白质。MGMT 启动子甲基化预测 HL 细胞对达卡巴嗪的敏感性，因此在 HL 患者中分析该因素可能很有趣。