Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and a variable risk of progression to acute myeloid leukemia (AML). Increasing evidence indicates that immune dysfunction is not merely a secondary phenomenon but a central biological feature across the MDS spectrum. Dysregulation affects both innate and adaptive immunity, including altered monocyte and dendritic cell function, impaired natural killer cell cytotoxicity, inflammasome activation, T-cell subset imbalance, and immune exhaustion phenotypes. These abnormalities are embedded within a chronically inflamed bone marrow microenvironment characterized by aberrant cytokine signaling, dysfunctional mesenchymal stromal support, and immune–clonal interactions that facilitate immune escape and immunoediting. Importantly, similar immune alterations are increasingly recognized in earlier clonal states such as clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS), suggesting a continuous immunopathological process.
This Research Topic aims to provide a comprehensive platform integrating mechanistic insights into immune dysfunction across the spectrum of clonal myeloid disorders, with a primary focus on MDS while incorporating early precursor states such as CHIP and CCUS. Although immune dysregulation is increasingly recognized as a defining biological component of MDS, its role in disease initiation, clonal expansion, phenotypic heterogeneity, progression, and therapeutic response remains incompletely characterized and insufficiently integrated into clinical decision-making frameworks.
By assembling state-of-the-art reviews and original research addressing molecular–immune interactions, immune microenvironment dynamics, standardized immune profiling methodologies, biomarker development, and therapeutic innovation—including immunomodulatory strategies and allogeneic hematopoietic stem cell transplantation as a model of immune-mediated disease control—this collection seeks to consolidate current knowledge and identify key gaps in the field.
Ultimately, the objective is to advance an integrated molecular–immune model of MDS pathobiology that informs risk stratification, therapeutic strategies, and the development of biomarker-driven precision medicine approaches.
This Research Topic welcomes original research articles, comprehensive reviews, and translational studies addressing immune dysfunction in MDS and related precursor conditions. Topics of interest include, but are not limited to:
• Immune–clonal interactions in CHIP and CCUS and their role in early disease evolution • Innate and adaptive immune dysfunction in MDS, including T-cell exhaustion, NK-cell, monocytes-DCs and MDSC impairment, inflammasome activation, and cytokine dysregulation • Bone marrow microenvironment dynamics: mesenchymal stromal cells, endothelial niches, MDSCs, and mechanisms of immune escape • Molecular–immune interfaces linking somatic mutations to immune phenotypes and clinical heterogeneity • Immune biomarkers for risk stratification, progression prediction, and therapeutic response • Standardization and harmonization of immune profiling methodologies • Immune modulation by conventional and targeted therapies • Immunotherapeutic strategies and emerging immune-based approaches • Allogeneic hematopoietic stem cell transplantation: immune reconstitution, graft-versus-leukemia effects, relapse biology, and immune-mediated complications
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This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
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