Do bone marrow fat cells or their precursors have a pathogenic role in idiopathic aplastic anaemia?

Idiopathic aplastic anaemia (AA), aplastic anaemia of unknown aetiology, is usually defined as marrow failure with fatty replacement of hemopoietic tissue and peripheral pancytopenia. The pathophysiology is largely unknown, though many mechanisms have been hypothesized. These include the absence of or defects in hemopoietic stem cells (HSC), abnormalities of the bone marrow (BM) microenvironment, immune system disorders and abnormalities of the regulatory factors that control hemopoiesis. The characteristic feature of AA is the replacement of hematopoietically active marrow by fat cells; however, the fat cells themselves have received little attention to date, and this apparent fatty marrow infiltration has been considered a secondary phenomenon. That the marrow fat cells in AA may be abnormal and may have a pathogenic role has never been considered. This communication, postulates that AA may result from an abnormal and excessive proliferation of marrow fat cells and the displacement of the hematopoietic tissue of the marrow; and that the resultant marrow failure could be a secondary phenomenon.