title: Immunologic aspects of hypoplastic myelodysplastic syndrome.
abstract: The pathophysiology of myelodysplastic syndromes (MDS) is multiple, complex, and poorly understood. In some cases of MDS, especially those in which the bone marrow is hypocellular, there is increasing experimental and clinical indication that an immune-mediated damage to hematopoietic precursors and changes in the hematopoiesis-supporting microenvironment contribute to disease development. Increased serum levels of type-1 cytokines, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), and oligoclonal expansion of cytotoxic T cells are observed in human MDS. In some cases, the immunologic attack to the marrow appears to be triggered by MDS-specific antigens, damaging the microenvironment and inducing cell apoptosis especially of normal progenitors. In murine models, dysregulation of osteoprogenitors leads to disrupted hematopoiesis of healthy hematopoietic progenitor and stem cells, eventually resulting in MDS and leukemia. In hypocellular MDS, marrow failure appears to be not only the result of ineffective erythropoiesis of abnormal clones, but also due to inhibition of normal progenitors. Immunosuppressive therapy with cyclosporine, anti-thymocyte globulin, or alemtuzumab may alleviate cytopenias and in some instances induce cytogenetic remission. However, not all patients respond to immunosuppression, and the identification of relevant biomarkers for an immune mechanism is necessary to identify those patients who may benefit from this treatment modality.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Calado
mesh_terms: D000741:Anemia, Aplastic / Q000175:diagnosis / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003937:Diagnosis, Differential; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D018579:Patient Selection; D055153:Stem Cell Niche / Q000276:immunology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents