Great importance in the course of chronic B-cell lymphocytic leukemia (B-CLL) has been ascribed to cytokines belonging to the superfamily of the tumor necrosis factor (TNF), including TRAIL (TNF-related apoptosis inducing ligand) and its specific receptors: TRAIL receptor 1 (TRAIL-R1), TRAIL receptor 2 (TRAIL-R2), TRAIL receptor 3 (TRAIL-R3), TRAIL receptor 4 (TRAIL-R4) and osteoprotegerin (OPG). Both the molecule and the receptors may occur in membrane and soluble forms, except for OPG which has only a soluble form. The aim of the study was to assess the levels of sTRAIL molecule and soluble TRAIL receptors - sTRAIL-R2 and OPG in the serum of patients with B-CLL. The findings revealed reduced concentrations of sTRAIL both before and after treatment and elevated levels of sTRAIL-R2 and OPG in patients before treatment. After treatment with CC (2CdA/Cladrybin and Cyklofosfamid) and FC (Fludarabin and Cyklofosfamid) we observed an increase in sTRAIL and a decrease in sTRAIL-R2. OPG levels were found to increase after treatment with CHOP (Vincristini, Cyklofosfamid, Adriamycin and Prednisol) and they decreased after administration of Leukeran (Chlorambucyl) and CMC (2CdA/Cladrybin, Mitoxanton and Cyklofosfamid). The relationships between TRAIL and its natural regulators in the serum of BCLL patients prior to treatment may impair apoptosis of leukemic B cells. Changes in these relationships after treatment with CC and FC seem to promote enhancement of apoptosis in these cells.
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Drug Discov Today
January 2025
Institute of Immunology, Kiel University (CAU), Kiel, Germany.
Death ligands (DLs), particularly tumor necrosis factor alpha (TNF-α), FAS ligand (FASL), and TNF-related apoptosis-inducing ligand (TRAIL), collectively termed TFT, are pivotal members of the TNF superfamily. While traditionally linked to apoptosis, TFT proteins have emerged as key regulators of various non-apoptotic processes. This review summarizes the non-apoptotic functions of TFT in cancer and explores the intricate crosstalk signaling pathways and their impact on nuclear factor kappa B (NF-κB) signaling, inflammation, and pro-tumorigenic function.
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Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
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Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
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