Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin

• Verfasst von: Dürr, Claudia [VerfasserIn]
• Verfasst von: Zenz, Thorsten [VerfasserIn]
• Titel: Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin
• Verf.angabe: Claudia Dürr, Bola S. Hanna, Angela Schulz, Fabienne Lucas, Manuela Zucknick, Axel Benner, Andrew Clear, Sibylle Ohl, Selcen Öztürk, Thorsten Zenz, Stephan Stilgenbauer, Min Li-Weber, Peter H. Krammer, John G. Gribben, Peter Lichter, Martina Seiffert
• E-Jahr: 2018
• Jahr: January 11, 2018
• Umfang: 10 S.
• Fussnoten: Gesehen am 25.06.2019
• Titel Quelle: Enthalten in: Haematologica
• Ort Quelle: Pavia : Ferrata Storti Foundation, 2014
• Jahr Quelle: 2018
• Band/Heft Quelle: 103(2018), 4, Seite 688-697
• ISSN Quelle: 1592-8721
• DOI: doi:10.3324/haematol.2017.177808
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1667905880

Abstract

Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors, and their deprivation has been identified as a promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of tumor necrosis factor (TNF) receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro, and an aberrantly high expression of this receptor in the proliferation centers of patients’ lymph nodes. Stimulation of TNF receptor-1 with TNF-α enhanced nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activity and viability of chronic lymphocytic leukemia cells, which was inhibited by wogonin. The therapeutic effects of wogonin were analyzed in mice after adoptive transfer of Eμ-T-cell leukemia 1 (TCL1) leukemic cells. Wogonin treatment prevented leukemia development when given early after transplantation. The treatment of full-blown leukemia resulted in the loss of the TNF receptor-1 on chronic lymphocytic leukemia cells and their mobilization to blood. Targeting TNF receptor-1 signaling is therefore proposed for the treatment of chronic lymphocytic leukemia.