Blöchl Constantin, Wang Di, Mayboroda Oleg A, Lageveen-Kammeijer Guinevere S M, Wuhrer Manfred
Center for Proteomics and Metabolomics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Cell Biosci. 2023 Feb 14;13(1):31. doi: 10.1186/s13578-023-00981-0.
Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous disease that has been suffering from stagnant survival curves for decades. In the endeavor toward improved diagnosis and treatment, cellular glycosylation has emerged as an interesting focus area in AML. While mechanistic insights are still limited, aberrant glycosylation may affect intracellular signaling pathways of AML blasts, their interactions within the microenvironment, and even promote chemoresistance. Here, we performed a meta-omics study to portray the glycomic landscape of AML, thereby screening for potential subtypes and responsible glyco-regulatory networks.
Initially, by integrating comprehensive N-, O-, and glycosphingolipid (GSL)-glycomics of AML cell lines with transcriptomics from public databases, we were able to pinpoint specific glycosyltransferases (GSTs) and upstream transcription factors (TFs) associated with glycan phenotypes. Intriguingly, subtypes M5 and M6, as classified by the French-American-British (FAB) system, emerged with distinct glycomic features such as high (sialyl) Lewis ((s)Le) and high sialylation, respectively. Exploration of transcriptomics datasets of primary AML cells further substantiated and expanded our findings from cell lines as we observed similar gene expression patterns and regulatory networks that were identified to be involved in shaping AML glycan signatures.
Taken together, our data suggest transcriptionally imprinted glycomic signatures of AML, reflecting their differentiation status and FAB classification. This study expands our insights into the emerging field of AML glycosylation and paves the way for studies of FAB class-associated glycan repertoires of AML blasts and their functional implications.
急性髓系白血病（AML）是一种在基因和表型上具有异质性的疾病，数十年来其生存率曲线一直停滞不前。在致力于改善诊断和治疗的过程中，细胞糖基化已成为AML中一个有趣的重点研究领域。虽然对其机制的了解仍然有限，但异常糖基化可能会影响AML原始细胞的细胞内信号通路、它们在微环境中的相互作用，甚至促进化疗耐药性。在此，我们进行了一项多组学研究，以描绘AML的糖组图谱，从而筛选潜在的亚型和相关的糖调控网络。
最初，通过将AML细胞系全面的N-、O-和糖鞘脂（GSL）糖组学与来自公共数据库的转录组学相结合，我们能够确定与聚糖表型相关的特定糖基转移酶（GST）和上游转录因子（TF）。有趣的是，按照法国-美国-英国（FAB）系统分类的M5和M6亚型分别呈现出独特的糖组学特征，如高（唾液酸化）Lewis（(s)Le）和高唾液酸化。对原发性AML细胞转录组数据集进行探索，进一步证实并扩展了我们从细胞系中获得的发现，因为我们观察到了类似的基因表达模式和调控网络，这些被确定参与塑造AML聚糖特征。
综上所述，我们的数据表明AML存在转录印记的糖组特征，反映了它们的分化状态和FAB分类。本研究扩展了我们对AML糖基化这一新兴领域的认识，并为研究AML原始细胞FAB类相关聚糖库及其功能意义铺平了道路。
