Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.
- Resource Type
- Academic Journal
- Authors
- Dürr C; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Hanna BS; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Schulz A; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Lucas F; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK.; Zucknick M; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Oslo Center for Biostatistics and Epidemiology; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway.; Benner A; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Clear A; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK.; Ohl S; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Öztürk S; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Zenz T; Molecular Therapy in Haematology and Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), and Department of Medicine V, University Hospital Heidelberg, Germany.; Stilgenbauer S; Internal Medicine III, University of Ulm, Germany.; Li-Weber M; Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Krammer PH; Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Gribben JG; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK.; Lichter P; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Seiffert M; Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany m.seiffert@dkfz.de.
- Source
- Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE
- Subject
- Language
- English
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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