Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin
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 reveal...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 11, 2018
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| In: |
Haematologica
Year: 2018, Volume: 103, Issue: 4, Pages: 688-697 |
| ISSN: | 1592-8721 |
| DOI: | 10.3324/haematol.2017.177808 |
| Online Access: | Verlag, Volltext: https://doi.org/10.3324/haematol.2017.177808 Verlag, Volltext: http://www.haematologica.org/content/103/4/688 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 25.06.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1592-8721 |
| DOI: | 10.3324/haematol.2017.177808 |