Pathogenesis of aplastic anemia.

Several assays were used to study myelopoiesis in 10 patients with aplastic anemia: the soft agar colony assay for granulocyte-monocyte progenitors; colony forming assay after removal of T lymphocytes; coculture of normal marrow with lymphocytes from normal individuals and patients; coculture of normal marrow with bone marrow fibroblasts from normal subjects and patients in the presence or absence of colony-stimulating factor. All patient assays revealed low colony formation. In two patients, colony formation by normal marrow cells in coculture with lymphocytes was suppressed with a colony count increase following T lymphocyte removal from marrow. Suppressor cells may have caused the aplasia in these patients. Most of the fibroblasts from normal individuals enhanced granulopoiesis in the absence of the colony-stimulating factor, while those from all patients failed to do so. When the colony-stimulating factor was present in the cultures, the degree of suppression of colony formation by fibroblasts derived from the patients was far greater than that by those from the healthy subjects. These results indicate that most aplastic anemias arise from defects of the stem cells and the bone marrow fibroblasts which hold major responsibilities in creating a microenvironment inductive to hematopoiesis.