Guirguis Andrew Adel
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; Department of Clinical Haematology, Austin Health, Heidelberg, Victoria, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
Exp Hematol. 2025 Mar;143:104694. doi: 10.1016/j.exphem.2024.104694. Epub 2024 Dec 6.
RNA methylation and the machinery that regulates or "reads" its expression has recently been implicated in the pathogenesis of acute myeloid leukemia (AML) and other hematologic malignancies. Modulation of these epigenetic marks has started to become a reality as several companies around the world seek to leverage this knowledge therapeutically in the clinic. Although the bases of observed activity in AML have been described by numerous groups, the exact context in which these therapies will ultimately be used remains to be properly determined. While context is likely to be of great importance here, a more "global" mechanism of action might allow for more widespread applicability to multiple disease subtypes. In other areas such as the myelodysplastic and other preleukemic syndromes, data remain sparse. Ongoing work is needed to determine whether therapeutic modulation of RNA modifications is a viable and biologically plausible approach in these cases. Regardless of the outcomes, this is an exciting era for "epitranscriptomics" as we navigate a pathway forward. Here, I describe the current knowledge around RNA methylation and hematologic malignancies at the end of 2024 including some of the relevant questions that are yet to be answered.
RNA甲基化以及调控或“读取”其表达的机制最近被认为与急性髓系白血病（AML）和其他血液系统恶性肿瘤的发病机制有关。随着全球几家公司试图在临床上利用这一知识进行治疗，对这些表观遗传标记的调控已开始成为现实。尽管许多研究小组已经描述了AML中观察到的活性基础，但这些疗法最终使用的确切背景仍有待确定。虽然背景在此可能非常重要，但更“全面”的作用机制可能会使这些疗法更广泛地适用于多种疾病亚型。在骨髓增生异常综合征和其他白血病前期综合征等其他领域，数据仍然稀少。需要持续开展工作来确定在这些情况下，对RNA修饰进行治疗性调控是否是一种可行且生物学上合理的方法。无论结果如何，在我们探索前进道路的过程中，这是“表观转录组学”的一个激动人心的时代。在此，我阐述了截至2024年底关于RNA甲基化和血液系统恶性肿瘤的现有知识，包括一些尚未解答的相关问题。
