Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 05253, Republic of Korea.
Int J Mol Sci. 2023 Jul 27;24(15):12037. doi: 10.3390/ijms241512037.
Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, effective treatments or expanded diagnostic or prognostic markers for AML have not yet been identified. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSCs) consist of hematopoietic stem cells (HSCs) and cancer cells transformed by a complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSCs dormancy and the diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML are discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSCs, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveal that microRNAs are a unique factor for LSCs. Multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSCs, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predict that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and could prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes achievable with Network Pharmacology research.
急性髓系白血病（AML）是最常见和最难治愈的白血病亚型。尽管对该疾病复杂的分子机制进行了广泛的研究，但尚未确定有效的治疗方法或扩展的 AML 诊断或预后标志物。AML 患者的形态学、免疫表型、细胞遗传学、生物分子和临床特征广泛而复杂。白血病干细胞（LSCs）由造血干细胞（HSCs）和癌细胞组成，它们之间通过复杂的、精细调节的相互作用而转化，导致 AML 的复杂性。本文综述了 LSCs 休眠的微环境调节及其对识别和靶向 LSCs 的诊断和治疗意义，因为它们在 AML 的发病机制中具有重要意义。认识 LSCs 和 HSCs 之间的关系至关重要，它们共同导致 AML 的进展。值得注意的是，甲基化是 AML 中一种重要的表观遗传变化，我们的数据还表明 microRNAs 是 LSCs 的一个独特因素。通过多靶点方法降低表观遗传因素的风险，例如通过天然化合物的局部 LSCs 消除，可能预防潜在致命的复发。此外，重叠基因的生存分析表明，特定靶标对患者的生存和预后有显著影响。我们预测，草药产品对表观遗传修饰的多靶点作用在 AML 中受到不同机制的控制，并可能预防潜在致命的复发。因此，这些策略可以促进将草药和天然化合物纳入网络药理学研究可实现的先进药物发现和开发过程。
