TY  - JOUR
AU  - Dürr, Claudia
AU  - Hanna, Bola
AU  - Schulz, Angela
AU  - Lucas, Fabienne
AU  - Zucknick, Manuela
AU  - Benner, Axel
AU  - Clear, Andrew
AU  - Ohl, Sibylle
AU  - Öztürk, Selcen
AU  - Zenz, Thorsten
AU  - Stilgenbauer, Stephan
AU  - Li-Weber, Min
AU  - Krammer, Peter
AU  - Gribben, John G
AU  - Lichter, Peter
AU  - Seiffert, Martina
TI  - Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.
JO  - Haematologica
VL  - 103
IS  - 4
SN  - 1592-8721
CY  - Pavia
PB  - Ferrata Storti Foundation
M1  - DKFZ-2018-00363
SP  - 688 - 697
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29326123
C2  - pmc:PMC5865430
DO  - DOI:10.3324/haematol.2017.177808
UR  - https://inrepo02.dkfz.de/record/132709
ER  -