APOPTOSIS RESISTANCE OF BLOOD-CELLS FROM PATIENTS WITH PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA, APLASTIC-ANEMIA, AND MYELODYSPLASTIC SYNDROME

Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal no cturnal hemoglobinuria (PNH). However, little is known about the molec ular events leading to the hypoplasia. Considering the close pathologi c association between PNH and aplastic anemia (AA), it is suggested th at a similar mechanism operates in the development of their BM failure . Recent reports have indicated apoptosis-mediated BM suppression in A A. It is thus conceivable that apoptosis also operates to cause BM hyp oplasia in PNH, if this is the case, PNH clones need to survive apopto sis and show considerable expansion leading to clinical manifestations . We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individual s to both spontaneous apoptosis without any ligands and that induced b y anti-FAS (CD95) antibody in vitro. The patients' BM CD34(+) cells we re also resistant to apoptosis induced by treatment with tumor necrosi s factor-alpha, interferon-gamma, and subsequently with anti FAS antib ody, In lymphocytes, the pathologic resistance was not discriminated f rom inherent resistance to apoptosis. Granulocytes from 13 patients wi th AA and 12 patients with myelodysplastic syndrome (MDS) exhibited si milar resistance to apoptosis. CD34(+) cells from MDS-BM also showed s imilar tendency. Thus, the comparative resistance to apoptosis support s the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders. (C) 1997 by The American Society of Hemat ology.