APO-1-induced apoptosis of leukemia cells from patients with adult T-cell leukemia.
The 48-Kd cell-surface protein APO-1 is a new member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 is expressed on various cells, including activated T and B cells and some lymphoid and nonlymphoid cell lines. Triggering of APO-1 by the monoclonal antibody anti-APO-1 induces programmed cell death (apoptosis) in APO-1-expressing cells. APO-1 is also present on T-cell lines derived from patients with adult T-cell leukemia (ATL). Therefore, we investigated APO-1 expression and APO-1-mediated induction of apoptosis ex vivo in cells from patients with ATL. Fresh leukemic cells from nine patients with ATL were assayed for APO-1 expression by two-color immunofluorescence. The leukemic cells from all patients strongly expressed APO-1. Incubation of ATL cells with anti-APO-1 in vitro inhibited spontaneous and cytokine-mediated DNA synthesis. Furthermore, DNA isolated from cells treated with anti-APO-1 exhibited polynucleosomal DNA fragmentation (DNA ladder) characteristic for apoptotic cell death. The analysis of APO-1-mediated apoptosis may represent a new approach to the study of growth control in lymphoid malignancies. In addition, induction of apoptosis by administration of anti-APO-1 may represent a new therapeutic approach for aggressive T-cell malignancies such as ATL.
Debatin
K M
KM
Oncology/Immunology Section, University Children's Hospital, Heidelberg, Germany.
Goldman
C K
CK
Waldmann
T A
TA
Krammer
P H
PH
D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D004249:DNA Damage; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D015458:Leukemia, T-Cell / Q000473:pathology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013997:Time Factors; D019014:fas Receptor
D000954:Antigens, Surface; D015375:Receptors, Interleukin-2; D019014:fas Receptor