APO-1-induced apoptosis of leukemia cells from patients with adult T-cell leukemia

• Published in: Blood Vol. 81; no. 11; pp. 2972 - 2977
• Main Authors: DEBATIN, K.-M, GOLDMAN, C. K, WALDMANN, T. A, KRAMMER, P. H
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01-06-1993
• Subjects: Antigens, Surface - physiology; Apoptosis; Biological and medical sciences; Cell Division; Cells, Cultured; DNA Damage; Dose-Response Relationship, Immunologic; fas Receptor; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunologic Techniques; In Vitro Techniques; Leukemia, T-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Receptors, Interleukin-2 - analysis; Time Factors; Human; Cell culture; Adult T cell leukemia; Malignant hemopathy; Gene expression; Tumor cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V81.11.2972.2972

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.