儿科急性淋巴细胞白血病的遗传和表观遗传靶向治疗。
Genetic and Epigenetic Targeting Therapy for Pediatric Acute Lymphoblastic Leukemia.
机构信息
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
出版信息
Cells. 2021 Nov 29;10(12):3349. doi: 10.3390/cells10123349.
Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, including DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in acute lymphoblastic leukemia. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.
急性淋巴细胞白血病是儿童最常见的恶性肿瘤，其特征是存在大量的遗传和表观遗传异常。表观遗传机制，包括 DNA 甲基化和组蛋白修饰，导致基因的可遗传沉默，而不改变其编码序列。新兴的研究增加了我们对白血病发生中表观遗传作用的理解，并表明 DNA 甲基化和组蛋白修饰作为谱系和亚型分类、预测复发以及急性淋巴细胞白血病疾病进展的生物标志物具有潜力。与遗传改变相比，用一些基于小分子的药物治疗时，表观遗传异常相对更易逆转。在这篇综述中，我们总结了 ALL 的遗传和表观遗传特征，并讨论了 DNA 甲基化和组蛋白修饰在预测复发中的未来作用，最后重点介绍了针对表观遗传改变的个体化和精准治疗。
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