N6-甲基腺苷 RNA 修饰在急性髓系白血病中的作用。
The N6-methyladenosine RNA modification in acute myeloid leukemia.
机构信息
Milner Therapeutics Institute, University of Cambridge, Puddicombe Way.
Haematological Cancer Genetics, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom.
出版信息
Curr Opin Hematol. 2021 Mar 1;28(2):80-85. doi: 10.1097/MOH.0000000000000636.
PURPOSE OF REVIEW
In recent years, the N6-methyladenosine (m6A) modification of RNA has been shown to play an important role in the development of acute myeloid leukemia (AML) and the maintenance of leukemic stem cells (LSCs). In this review we summarise the recent findings in the field of epitranscriptomics related to m6A and its relevance in AML.
RECENT FINDINGS
Recent studies have focused on the role of m6A regulators in the development of AML and their potential as translational targets. The writer Methyltransferase Like 3 and its binding partner Methyltransferase Like 14, as well as the reader YTH domain-containing family protein 2, were shown to be vital for LSC survival, and their loss has detrimental effects on AML cells. Similar observations were made with the demethylases fat mass and obesity-associated protein and AlkB homologue 5 RNA demethylase. Of importance, loss of any of these genes has little to no effect on normal hemopoietic stem cells, suggesting therapeutic potential.
SUMMARY
The field of epitranscriptomics is still in its infancy and the importance of m6A and other RNA-modifications in AML will only come into sharper focus. The development of therapeutics targeting RNA-modifying enzymes may open up new avenues for treatment of such malignancies.
综述目的：近年来，RNA 的 N6-甲基腺苷（m6A）修饰被证明在急性髓系白血病（AML）的发展和白血病干细胞（LSCs）的维持中起着重要作用。在这篇综述中，我们总结了与 m6A 及其在 AML 中的相关性相关的转录后修饰领域的最新发现。
最近的发现：最近的研究集中在 m6A 调节剂在 AML 发展中的作用及其作为转化靶点的潜力。甲基转移酶样蛋白 3 及其结合伴侣甲基转移酶样蛋白 14，以及读者 YTH 结构域家族蛋白 2，被证明对 LSC 存活至关重要，其缺失对 AML 细胞有不利影响。类似的观察结果也在去甲基酶肥胖相关蛋白和 AlkB 同源物 5 RNA 去甲基酶中得到了证实。重要的是，这些基因中的任何一个缺失对正常造血干细胞几乎没有影响，这表明了其治疗潜力。
总结：转录后修饰领域仍处于起步阶段，m6A 和其他 RNA 修饰在 AML 中的重要性将更加凸显。针对 RNA 修饰酶的治疗方法的开发可能为治疗这些恶性肿瘤开辟新的途径。
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