Uncontrolled triggering of programmed cell death (apoptosis) in haematopoietic stem cells: a new hypothesis for the pathogenesis of aplastic anaemia.

The cause of bone marrow failure in aplastic anaemia (AA) is still unknown; however, it is clear that acquired AA is a heterogeneous disease including basically different pathophysiological conditions. Causative agents, clinically associated with AA, possibly exert their action through restricted pathways. Some theoretical and experimental data show that programmed cell death (PCD) or apoptosis is physiologically important in normal haematopoiesis and could be involved in the pathophysiological events responsible for the development of AA. Therefore, it is intriguing to hypothesize that the pathogenetic mechanism underlying most cases of acquired AA could be represented by an excessive and/or uncontrolled triggering of PCD in haematopoietic stem cells. Investigations to test this hypothesis are proposed.