Editorial: The pathogenesis of aplastic anemia: a defective pluripotent hematopoietic stem cell with inappropriate balance of differentiation and self-replication

Abstract

Aplastic anemia most commonly is defined as a condition characterized by reduced numbers of red cells, neutrophils and platelets in the blood in the presence of a hypocellular bone marrow. In most patients it is drug induced. Aplastic anemia may also occur in association with infectious hepatitis, as an inherited disease or as an idiopathic disease in which no cause for marrow insult can be identified. Pancytopenia and hypoplasia of the marrow which persists for prolonged periods following withdrawal of offending agents may be due to an abnormality of pluripotent stem cells as well as to an initial reduction in their number. This abnormality is one in which inappropriate differentiation of pluripotent cells into mature myeloid lines occurs. For the pluripotent compartment to regenerate to normal size, the proportion of stem cells which self-replicate must exceed the proportion which differentiate. In the mouse, there is a poorly defined control system which leads to self-replication far in excess of differentiation when the stem cell compartment is severely reduced. Stem cells may be damaged in certain cases of human aplasia so that the rate of self-replication fails to exceed the rate of differentiation and, as a consequence, the hypoplasia persists.