Xu Zi-Jun, Wen Xiang-Mei, Zhang Yuan-Cui, Jin Ye, Ma Ji-Chun, Gu Yu, Chen Xin-Yi, Xia Pei-Hui, Qian Wei, Lin Jiang, Qian Jun
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
Zhenjiang Clinical Research Center of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
Front Genet. 2022 Aug 10;13:948079. doi: 10.3389/fgene.2022.948079. eCollection 2022.
RNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully elucidated in acute myeloid leukemia (AML). In our study, we explored the genetic and transcriptional alterations of 23 m6A regulators in AML patients. Three distinct molecular subtypes were identified and associated with prognosis, patient clinicopathological features, as well as TME characteristics. The TME characterization revealed that m6A patterns were highly connected with metabolic pathways such as biosynthesis of unsaturated fatty acids, cysteine and methionine metabolism, and citrate cycle TCA cycle. Then, based on the differentially expressed genes (DEGs) related to m6A molecular subtypes, our study categorized the entire cohort into three m6A gene clusters. Furthermore, we constructed the m6Ascore for quantification of the m6A modification pattern of individual AML patients. It was found that the tumor-infiltrating lymphocyte cells (TILs) closely correlated with the three m6A clusters, three m6A gene clusters, and m6Ascore. And many biological processes were involved, including glycogen degradation, drug metabolism by cytochrome P450, pyruvate metabolism, and so on. Our comprehensive analysis of m6A regulators in AML demonstrated their potential roles in the clinicopathological features, prognosis, tumor microenvironment, and particularly metabolic pathways. These findings may improve our understanding of m6A regulators in AML and offer new perspectives on the assessment of prognosis and the development of anticancer strategy.
RNA N6-甲基腺嘌呤（m6A）是最常见且研究最深入的RNA修饰，它对RNA代谢、细胞信号传导、细胞存活和分化起着关键调节作用。然而，多种m6A调节因子在急性髓系白血病（AML）肿瘤微环境（TME）中的整体作用尚未完全阐明。在我们的研究中，我们探索了AML患者中23种m6A调节因子的基因和转录改变。识别出三种不同的分子亚型，它们与预后、患者临床病理特征以及TME特征相关。TME特征分析显示，m6A模式与不饱和脂肪酸生物合成、半胱氨酸和甲硫氨酸代谢以及柠檬酸循环（TCA循环）等代谢途径高度相关。然后，基于与m6A分子亚型相关的差异表达基因（DEG），我们的研究将整个队列分为三个m6A基因簇。此外，我们构建了m6A评分来量化个体AML患者的m6A修饰模式。发现肿瘤浸润淋巴细胞（TIL）与三个m6A簇、三个m6A基因簇和m6A评分密切相关。并且涉及许多生物学过程，包括糖原降解、细胞色素P450介导的药物代谢、丙酮酸代谢等。我们对AML中m6A调节因子的综合分析证明了它们在临床病理特征、预后、肿瘤微环境，特别是代谢途径中的潜在作用。这些发现可能会增进我们对AML中m6A调节因子的理解，并为预后评估和抗癌策略的制定提供新的视角。
