Epigenetics encompasses heritable and stable changes in gene expression caused by external chromosomal modifications, without altering the underlying DNA sequence. Epigenetic modifications, established during early development and maintained through successive cell divisions, play a critical role in regulating gene expression. Post-translational modifications (PTMs) are a key aspect of epigenetics and are essential for modulating protein functionality, as well as regulatory cellular processes, including proliferation, differentiation, metabolic pathways, and tumorigenic events. Among these, the small ubiquitin-related modifier (SUMOylation) system is a reversible PTM mechanism that alters target protein interaction surfaces through covalent binding to lysine residues, thereby influencing protein structure and function. Acute myeloid leukemia (AML) is a highly aggressive malignancy characterized by the clonal expansion of primitive hematopoietic stem cells of the myeloid lineage in the bone marrow. Despite recent advancements in therapeutic strategies and an improved understanding of leukemogenic pathways, patient outcomes remain poor, particularly in elderly populations. Consequently, efforts have focused on developing novel agents, including co-targeting specific mutations or integrating targeted therapies into combinatorial chemotherapeutic regimens. Emerging evidence suggests that SUMOylation plays a significant role in AML pathogenesis and treatment response, representing a promising therapeutic target for advanced disease cases. This review provides a brief analysis of the functional role of the SUMOylation system in AML and highlights its potential as a therapeutic target. We also discuss current knowledge gaps and propose directions for future research to advance precision medicine approaches for AML treatment.
表观遗传学涉及由外部染色体修饰引起的基因表达可遗传且稳定的变化，而不改变其DNA序列。表观遗传修饰在早期发育阶段建立，并通过连续细胞分裂得以维持，在调控基因表达中发挥关键作用。翻译后修饰是表观遗传学的重要方面，对于调节蛋白质功能以及调控细胞过程（包括增殖、分化、代谢途径和肿瘤发生事件）至关重要。其中，小泛素相关修饰物系统是一种可逆的翻译后修饰机制，通过共价结合赖氨酸残基改变靶蛋白相互作用表面，从而影响蛋白质结构和功能。急性髓系白血病是一种高度侵袭性恶性肿瘤，其特征是骨髓中髓系原始造血干细胞的克隆性扩增。尽管近年来治疗策略有所进展，对白血病发生途径的理解也有所加深，但患者预后仍然较差，尤其是在老年人群中。因此，研究重点已转向开发新型药物，包括共同靶向特定突变或将靶向疗法整合到联合化疗方案中。新出现的证据表明，SUMOylation在AML的发病机制和治疗反应中起着重要作用，为晚期疾病病例提供了一个有前景的治疗靶点。本综述简要分析了SUMOylation系统在AML中的功能作用，并强调了其作为治疗靶点的潜力。我们还讨论了当前的知识空白，并提出了未来研究的方向，以推进AML治疗的精准医学方法。
Diagnostic and Therapeutic Implications of the SUMOylation Pathway in Acute Myeloid Leukemia
肿瘤(癌症)患者之家