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 nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH. If this is the case, PNH clones need to survive apoptosis 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 individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34+ cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti-FAS antibody. In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34+ cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders.
Horikawa
K
K
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Nakakuma
H
H
Kawaguchi
T
T
Iwamoto
N
N
Nagakura
S
S
Kagimoto
T
T
Takatsuki
K
K
D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma