%0 Journal Article
%A Dürr, Claudia
%A Hanna, Bola
%A Schulz, Angela
%A Lucas, Fabienne
%A Zucknick, Manuela
%A Benner, Axel
%A Clear, Andrew
%A Ohl, Sibylle
%A Öztürk, Selcen
%A Zenz, Thorsten
%A Stilgenbauer, Stephan
%A Li-Weber, Min
%A Krammer, Peter
%A Gribben, John G
%A Lichter, Peter
%A Seiffert, Martina
%T Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.
%J Haematologica
%V 103
%N 4
%@ 1592-8721
%C Pavia
%I Ferrata Storti Foundation
%M DKFZ-2018-00363
%P 688 - 697
%D 2018
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:29326123
%2 pmc:PMC5865430
%R 10.3324/haematol.2017.177808
%U https://inrepo02.dkfz.de/record/132709