Drożak Paulina, Bryliński Łukasz, Zawitkowska Joanna
Student Scientific Society, Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland.
Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland.
Cancers (Basel). 2022 Nov 1;14(21):5384. doi: 10.3390/cancers14215384.
Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced by epigenetic modifications. These changes include: DNA hypermethylation, histone modification and miRNA alteration. DNA hypermethylation in promoter regions, which leads to silencing of tumor suppressor genes, is a common epigenetic alteration in ALL. Histone modifications are mainly caused by an increased expression of histone deacetylases. A dysregulation of miRNA results in changes in the expression of their target genes. To date, several hundred genes were identified as suppressed by epigenetic mechanisms in ALL. What is promising is that epigenetic alterations in ALL may be used as potential biomarkers for classification of subtypes, predicting relapse and disease progression and assessing minimal residual disease. Furthermore, since epigenetic lesions are potentially reversible, an activation of epigenetically silenced genes with the use of hypomethylating agents or histone deacetylase inhibitors may be utilized as a therapeutic strategy for ALL. The following review summarizes our current knowledge about epigenetic modifications in ALL and describes potential uses of epigenetics in the clinical management of this disease.
近年来，我们对儿童急性淋巴细胞白血病（ALL）的认识有了新的见解，同时出现了几种突破性的治疗方法。然而，这种疾病背后机制的多个方面仍有待阐明。有证据表明，ALL中的白血病发生受到表观遗传修饰的广泛影响。这些变化包括：DNA高甲基化、组蛋白修饰和miRNA改变。启动子区域的DNA高甲基化导致肿瘤抑制基因沉默，是ALL中常见的表观遗传改变。组蛋白修饰主要由组蛋白脱乙酰酶表达增加引起。miRNA失调导致其靶基因表达发生变化。迄今为止，数百个基因被确定在ALL中受表观遗传机制抑制。有前景的是，ALL中的表观遗传改变可作为亚型分类、预测复发和疾病进展以及评估微小残留病的潜在生物标志物。此外，由于表观遗传损伤可能是可逆的，使用去甲基化剂或组蛋白脱乙酰酶抑制剂激活表观遗传沉默的基因可作为ALL的一种治疗策略。以下综述总结了我们目前对ALL中表观遗传修饰的认识，并描述了表观遗传学在该疾病临床管理中的潜在用途。
