Emerging Insights into Molecular Mechanisms of Inflammation in Myelodysplastic Syndromes

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.

Automated summary

Inflammation has a significant impact on human hematopoiesis, particularly in regulating the homeostasis of hematopoietic stem cells. Dysregulated inflammation can lead to abnormal hematopoiesis and may be involved in the pathogenesis of diseases such as myelodysplastic syndromes. Recent studies have used single-cell sequencing and multi-omic approaches to investigate the cellular heterogeneity and gene expression of hematopoietic stem cells in normal and malignant conditions, shedding light on the mechanisms underlying inflammatory signaling and immune response activation in MDS progression.