Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) differentially regulate apoptosis in normal and neoplastic human basophils

• Published in: Leukemia & lymphoma Vol. 54; no. 4; pp. 835 - 842
• Main Authors: Förster, Anja, Falcone, Franco H., Gibbs, Bernhard F., Preussner, Liane M., Fiebig, Britta S., Altunok, Hülya, Seeger, Jens M., Cerny-Reiterer, Sabine, Rabenhorst, Anja, Papenfuss, Kerstin, Valent, Peter, Kashkar, Hamid, Hartmann, Karin
• Format: Journal Article
• Language: English
• Published: United States Informa Healthcare 01.04.2013; Taylor & Francis
• Subjects: Antibodies, Monoclonal - pharmacology; Apoptosis; Apoptosis - drug effects; basophils; Basophils - drug effects; Basophils - metabolism; Basophils - pathology; CD95; Cell Line; Cell Survival - drug effects; chronic myeloid leukemia; Cyclohexanes; fas Receptor - antagonists & inhibitors; fas Receptor - metabolism; Humans; Neoplasms - metabolism; Neoplasms - pathology; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2012.731600

Abstract Basophilia is associated with allergic and parasitic diseases and advanced chronic myeloid leukemia. In the present study, we characterized the expression and function of the death receptors Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in basophils from healthy donors compared to neoplastic basophils. Peripheral blood basophils obtained from healthy donors (HD-PBB) and from patients with chronic myeloid leukemia (CML-PBB) were found to express high levels of Fas/CD95 and low levels of TRAIL-R2, whereas the basophil-like chronic myeloid leukemia cell line KU-812 expressed significant levels of TRAIL-R1 and TRAIL-R2. HD-PBB underwent apoptosis in response to anti-Fas/CD95, but showed resistance to TRAIL, unless they were co-treated with actinomycin D. Interestingly, CML-PBB and KU-812 cells exhibited the opposite response pattern with resistance to anti-Fas/CD95, but significant susceptibility to TRAIL-induced apoptosis. Our data show that anti-Fas/CD95 and TRAIL differentially regulate apoptosis of normal and neoplastic human basophils, which may direct the development of novel therapeutic strategies.