Cao Lin-Lin, Liu Hangqi, Yue Zhihong, Pei Lin, Wang Hui, Jia Mei
a Department of Clinical Laboratory , Peking University People's Hospital , Beijing , People's Republic of China.
Hematology. 2019 Dec;24(1):567-576. doi: 10.1080/16078454.2019.1642563.
DNA methylation is a well-known epigenetic modification, and it can be iteratively oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Acute lymphoblastic leukemia (ALL) is a severe hematological disease, and it is essential to find out new biomarkers to better diagnose and cure ALL due to the development of chemo-resistance and low cure rate in adult ALL. This study aims to describe the role of global methylation and demethylation intermediates in ALL. The levels of global methylation and its oxidation products in the peripheral blood (PB) of ALL patients and healthy controls were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In this study, we described that global 5-mC, 5-hmC and 5-fC levels were dysregulated in ALL, and they were associated with clinical characteristics and genetic abnormalities of ALL patients. Interestingly, 5-mC and 5-hmC were closely related to inflammation, and the levels of 5-hmC were inversely correlated with C-Reactive protein (CRP) and ferritin. Finally, 5-mC and 5-hmC were associated with complete remission (CR), and 5-hmC was revealed as an independent prognostic indicator for ALL. This study described a novel role for global methylation and demethylation intermediates in ALL detection and prognosis, and provided new clue to distinguish high-risk patients and improve the curative effect on ALL patients.
DNA甲基化是一种众所周知的表观遗传修饰，它可以被反复氧化为5-羟甲基胞嘧啶（5-hmC）、5-甲酰基胞嘧啶（5-fC）和5-羧基胞嘧啶（5-caC）。急性淋巴细胞白血病（ALL）是一种严重的血液疾病，由于成人ALL化疗耐药性的发展和治愈率低，找出新的生物标志物以更好地诊断和治疗ALL至关重要。本研究旨在描述整体甲基化和去甲基化中间体在ALL中的作用。通过酶联免疫吸附测定（ELISA）测定ALL患者和健康对照外周血（PB）中整体甲基化及其氧化产物的水平。在本研究中，我们描述了ALL中整体5-mC、5-hmC和5-fC水平失调，并且它们与ALL患者的临床特征和基因异常相关。有趣的是，5-mC和5-hmC与炎症密切相关，5-hmC水平与C反应蛋白（CRP）和铁蛋白呈负相关。最后，5-mC和5-hmC与完全缓解（CR）相关，并且5-hmC被揭示为ALL的独立预后指标。本研究描述了整体甲基化和去甲基化中间体在ALL检测和预后中的新作用，并为区分高危患者和提高ALL患者的治疗效果提供了新线索。
