K. Horikawa et al., APOPTOSIS RESISTANCE OF BLOOD-CELLS FROM PATIENTS WITH PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA, APLASTIC-ANEMIA, AND MYELODYSPLASTIC SYNDROME, Blood, 90(7), 1997, pp. 2716-2722
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.