Vallelonga Veronica, Gandolfi Francesco, Ficara Francesca, Della Porta Matteo Giovanni, Ghisletti Serena
Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, 20139 Milan, Italy.
Milan Unit, CNR-IRGB, 20090 Milan, Italy.
Biomedicines. 2023 Sep 23;11(10):2613. doi: 10.3390/biomedicines11102613.
Inflammation impacts human hematopoiesis across physiologic and pathologic conditions, as signals derived from the bone marrow microenvironment, such as pro-inflammatory cytokines and chemokines, have been shown to alter hematopoietic stem cell (HSCs) homeostasis. Dysregulated inflammation can skew HSC fate-related decisions, leading to aberrant hematopoiesis and potentially contributing to the pathogenesis of hematological disorders such as myelodysplastic syndromes (MDS). Recently, emerging studies have used single-cell sequencing and muti-omic approaches to investigate HSC cellular heterogeneity and gene expression in normal hematopoiesis as well as in myeloid malignancies. This review summarizes recent reports mechanistically dissecting the role of inflammatory signaling and innate immune response activation due to MDS progression. Furthermore, we highlight the growing importance of using multi-omic techniques, such as single-cell profiling and deconvolution methods, to unravel MDSs' heterogeneity. These approaches have provided valuable insights into the patterns of clonal evolution that drive MDS progression and have elucidated the impact of inflammation on the composition of the bone marrow immune microenvironment in MDS.
在生理和病理条件下，炎症都会影响人类造血，因为骨髓微环境衍生的信号，如促炎细胞因子和趋化因子，已被证明会改变造血干细胞（HSC）的稳态。炎症失调会扭曲HSC命运相关的决定，导致异常造血，并可能促成血液系统疾病如骨髓增生异常综合征（MDS）的发病机制。最近，新兴研究使用单细胞测序和多组学方法来研究正常造血以及髓系恶性肿瘤中HSC的细胞异质性和基因表达。本综述总结了最近关于从机制上剖析炎症信号传导和由于MDS进展导致的先天免疫反应激活作用的报告。此外，我们强调了使用多组学技术（如单细胞分析和反卷积方法）来揭示MDS异质性的重要性日益增加。这些方法为驱动MDS进展的克隆进化模式提供了有价值的见解，并阐明了炎症对MDS中骨髓免疫微环境组成的影响。
