THE ENIGMA OF THE APLASTIC ANEMIA/PNH SYNDROME

摘要

Summary: Bone marrow failure has been regarded as one consequence of paroxysmal nocturnal hemoglobinuria (PNH), and PNH in turn has been described as a late event in patients recovering from aplastic anemia. Better understanding of the pathophysiology of both diseases and improved tests for cell surface glycosylphosphatidylinositol (GPI)-linked proteins have radically altered this view. How cytometry of granulocytes shows evidence of an expanded PNH clone in a large proportion of marrow failure patients at the time of presentation: in our large NIH series, about 1/3 of over 200 aplastic anemia cases and almost 20% of more than 100 myelodysplasia cases. Clonal PNH expansion (rather than bone marrow failure) is strongly linked to the histocompatability antigen H.A.-DR2 in all clinical varieties of the disease, suggesting a relationship to the immune pathophysiology. An extrinsic mechanism of clonal expansion is also more consistent with knock-out mouse models and culture experiments with primary cellsand cell lines, which have failed to demonstrate an intrinsic proliferative advantage for PNH cells.