title: Pathophysiologic mechanisms in acquired aplastic anemia.
abstract: Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Absence of hematopoietic cells has been recognized from the characteristic morphology for a century; an immune pathophysiology has been inferred from improvement in blood counts with immunosuppressive therapy in the majority of patients. Molecular mechanisms underlying both T cell effector cells and the target marrow stem and progenitor cells are now being identified. Activated type 1 cytotoxic T cells and type 1 cytokines have been implicated in cell culture experiments; clues to the molecular basis of the aberrant immune response include cytokine gene polymorphisms and abnormalities in the regulatory pathways for gamma-interferon. For stem cell depletion, mutations in genes of the telomere repair complex are present in some patients with apparently acquired aplastic anemia. Telomerase deficiency is associated with short telomeres and a quantitative reduction in marrow progenitors and likely also a qualitative deficiency in the repair capacity of hematopoietic tissue.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20891, USA. youngns@mail.nih.gov
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes; D019098:Telomerase / Q000172:deficiency
chemical_list: D016207:Cytokines; D019098:Telomerase