Pathophysiology of acquired aplastic anemia. The figure stresses the crucial and related roles of the hematopoietic stem-cell compartment as a target for the immune response. An inciting event, such as a virus or medical drug, provokes an aberrant immune response, triggering oligoclonal expansion of cytotoxic T cells that destroy hematopoietic stem cells (left panel, Onset). Bone marrow transplantation or immunosuppressive therapy leads to complete response (CR) or partial response (PR) by eradicating or suppressing pathogenic T-cell clones (middle panel, Recovery). Relapse occurs with recurrence of the immune response, and the immunologically stressed and depleted stem-cell compartment also allows selection of abnormal hematopoietic clones that manifest as paroxysmal nocturnal hemoglobinuria, myelodysplasia (MDS), and occasionally acute myelogenous leukemia (AML) (right panel, Late Disease).