ETIOLOGY, PATHOGENESIS AND TREATMENT OF APLASTIC ANEMIA

再生障碍性贫血的病理生理学仍不清楚，但骨髓

The pathophysiology of aplastic anemia remains obscure but bone marrow transplantation and more recently therapy with anti-thymocyte or anti-lymphocyte globulin have proved clinically effective. This research program is designed to investigate the role of suppressor cells in so-called "immune" aplastic anemia, to determine the phenotypic characteristics of such cells using a panel of monoclonal antibodies, to amplify autoreactive cells using Interleukin 2 and to determine the nature of the cell population being suppressed. Attention will be directed at suppressor mechanisms acting upon accessory cells producing hematopoietic growth regulatory factors such as colony stimulating factors or inhibitory activities such as acidic isoferritin. Assays for pluripotential stem cells, both clonal and in suspension culture, will be used to detect suppressor cells and regulatory factor dysfunction where the primary target is the stem cell. An additional objective is to define the role of the human bone marrow microenvironmental cells on the proliferation and differentiation of hematopoietic stem cells using marrow from untreated aplastics and from patients recovering from bone marrow transplantation or ATG therapy. Well defined in vitro assays will be employed to assess the changes occurring in the number and hemopoietic function of marrow fibroblasts, endothelial cells, adipocytes and macrophage-derived lipid containing cells. Analysis of these changes will allow determination of 1) aplasia primarily due to environmental defects; 2) aplasia due to autoreactive cells compromising microenvironmental function; 3) the influence of immunosuppression and/or cytoreduction or transplantation on the integrity of the microenvironment.