Helmer Jordan A, Iraburu Rocio, Tirado Carlos A
The International Circle of Genetic Studies, Minnesota Chapter, Minneapolis, MN.
Allina Health, Minneapolis, MN, USA.
J Assoc Genet Technol. 2019;45(1):10-13.
Precursor B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common neoplasms. It is characterized by genetic and epigenetic aberrations. The most remarkable mechanisms involved in epigenetic abnormalities are DNA methylation and acetylation. Methylation of CpG islands in promoter regions and acetylation of lysine residues regulate gene expression. Several studies have shown that patients with B-ALL show aberrant DNA methylation in a genome-wide scale. Histone deacetylases (HDAC) regulate gene expression by removing acetyl groups from lysine residues and histone acetyltransferase (HAT) adds acetyl groups. A hematologic malignancy like B-ALL may be very sensitive to small-molecule inhibitors that target these epigenetic mechanisms and therefore may induce expression of pro-apoptotic factors. Thus, HDAC inhibitors (HDACi), DNA methyltransferase inhibitors (DNMTi) and histone acetyltransferase inhibitors (HATi) have been developed as therapies. The objective of this review is to summarize the different epigenetic mechanisms involved in B-ALL.
前体B细胞急性淋巴细胞白血病（B-ALL）是最常见的肿瘤之一。其特征在于遗传和表观遗传畸变。参与表观遗传异常的最显著机制是DNA甲基化和乙酰化。启动子区域中CpG岛的甲基化和赖氨酸残基的乙酰化调节基因表达。多项研究表明，B-ALL患者在全基因组范围内存在异常的DNA甲基化。组蛋白脱乙酰酶（HDAC）通过从赖氨酸残基上去除乙酰基来调节基因表达，而组蛋白乙酰转移酶（HAT）则添加乙酰基。像B-ALL这样的血液系统恶性肿瘤可能对靶向这些表观遗传机制的小分子抑制剂非常敏感，因此可能诱导促凋亡因子的表达。因此，组蛋白脱乙酰酶抑制剂（HDACi）、DNA甲基转移酶抑制剂（DNMTi）和组蛋白乙酰转移酶抑制剂（HATi）已被开发为治疗方法。本综述的目的是总结B-ALL中涉及的不同表观遗传机制。
