磷脂酶 A2 受体 1 启动子区域甲基化在儿童 B 细胞急性淋巴细胞白血病中的作用。

Methylation of the Phospholipase A2 Receptor 1 Promoter Region in Childhood B Cell Acute Lymphoblastic Leukaemia.

机构信息

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University of Dresden, 01307, Dresden, Germany.

Department of Paediatrics, University Hospital Carl Gustav Carus, Technical University of Dresden, 01307, Dresden, Germany.

出版信息

Sci Rep. 2020 Jun 3;10(1):9058. doi: 10.1038/s41598-020-65825-0.

DOI:10.1038/s41598-020-65825-0

PMID:32493972

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7270080/

Abstract

Acute lymphoblastic leukaemia (ALL) is the most common form of paediatric cancer and epigenetic aberrations are determinants of leukaemogenesis. The aim of this study was to investigate the methylation degree of a distinct phospholipase A2 receptor 1 (PLA2R1) promoter region in paediatric ALL patients and to evaluate its relevance as new biomarker for monitoring treatment response and burden of residual disease. The impact of PLA2R1 re-expression on proliferative parameters was assessed in vitro in Jurkat cells with PLA2R1 naturally silenced by DNA methylation. Genomic DNA was isolated from bone marrow (BM) and peripheral blood (PB) of 44 paediatric ALL patients. PLA2R1 methylation was analysed using digital PCR and compared to 20 healthy controls. Transfected Jurkat cells were investigated using cell growth curve analysis and flow cytometry. PLA2R1 was found hypermethylated in BM and PB from pre-B and common ALL patients, and in patients with the disease relapse. PLA2R1 methylation decreased along with leukaemic blast cell reduction during ALL induction treatment. In vitro analysis revealed an anti-proliferative phenotype associated with PLA2R1 re-expression, suggesting a tumour-suppressive function of PLA2R1. Collected data indicates that PLA2R1 promoter methylation quantitation can be used as biomarker for ALL induction treatment control, risk stratification, and early detection of ALL relapse.

摘要

急性淋巴细胞白血病（ALL）是儿童中最常见的癌症形式，表观遗传异常是白血病发生的决定因素。本研究旨在探讨儿科 ALL 患者中特定磷脂酶 A2 受体 1（PLA2R1）启动子区域的甲基化程度，并评估其作为监测治疗反应和残留疾病负担的新生物标志物的相关性。通过 DNA 甲基化自然沉默 Jurkat 细胞中的 PLA2R1，评估 PLA2R1 再表达对体外增殖参数的影响。从 44 名儿科 ALL 患者的骨髓（BM）和外周血（PB）中分离基因组 DNA。使用数字 PCR 分析 PLA2R1 甲基化，并与 20 名健康对照进行比较。使用细胞生长曲线分析和流式细胞术研究转染的 Jurkat 细胞。在 pre-B 和常见 ALL 患者以及疾病复发患者的 BM 和 PB 中发现 PLA2R1 高度甲基化。随着 ALL 诱导治疗中白血病母细胞的减少，PLA2R1 甲基化减少。体外分析显示 PLA2R1 再表达与抗增殖表型相关，表明 PLA2R1 具有肿瘤抑制功能。收集的数据表明，PLA2R1 启动子甲基化定量可作为 ALL 诱导治疗控制、风险分层和 ALL 复发早期检测的生物标志物。