Bone Marrow Immune Microenvironment in Myelodysplastic Syndromes.

Simple Summary: The bone marrow (BM) microenvironment regulates normal hematopoiesis and exerts variable activity in various inflammatory, toxic, autoimmune, or neoplastic diseases and conditions. Most importantly, it has a major role in the pathogenesis of BM failure syndromes and particularly of myelodysplastic syndromes (MDS), in which it is dynamically implicated in the early phase of their pathogenesis, as well as in their course and evolution. This review presents a concise overview of the literature, highlighting the impact of the immune component of the BM microenvironment during normal hematopoiesis, in chronic inflammatory states, and in low- and high-risk MDS, laying the ground for further research on the cellular and biochemical immune parameters that participate in early stages of MDS pathogenesis and in disease evolution. The BM, the major hematopoietic organ in humans, consists of a pleiomorphic environment of cellular, extracellular, and bioactive compounds with continuous and complex interactions between them, leading to the formation of mature blood cells found in the peripheral circulation. Systemic and local inflammation in the BM elicit stress hematopoiesis and drive hematopoietic stem cells (HSCs) out of their quiescent state, as part of a protective pathophysiologic process. However, sustained chronic inflammation impairs HSC function, favors mutagenesis, and predisposes the development of hematologic malignancies, such as myelodysplastic syndromes (MDS). Apart from intrinsic cellular mechanisms, various extrinsic factors of the BM immune microenvironment (IME) emerge as potential determinants of disease initiation and evolution. In MDS, the IME is reprogrammed, initially to prevent the development, but ultimately to support and provide a survival advantage to the dysplastic clone. Specific cellular elements, such as myeloid-derived suppressor cells (MDSCs) are recruited to support and enhance clonal expansion. The immune-mediated inhibition of normal hematopoiesis contributes to peripheral cytopenias of MDS patients, while immunosuppression in late-stage MDS enables immune evasion and disease progression towards acute myeloid leukemia (AML). In this review, we aim to elucidate the role of the mediators of immune response in the initial pathogenesis of MDS and the evolution of the disease. [ABSTRACT FROM AUTHOR]

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