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000132709 0247_ $$2doi$$a10.3324/haematol.2017.177808
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000132709 0247_ $$2ISSN$$a1592-8721
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000132709 1001_ $$0P:(DE-HGF)0$$aDürr, Claudia$$b0$$eFirst author
000132709 245__ $$aTumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.
000132709 260__ $$aPavia$$bFerrata Storti Foundation$$c2018
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000132709 520__ $$aChronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors, and their deprivation has been identified as a promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of tumor necrosis factor (TNF) receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro, and an aberrantly high expression of this receptor in the proliferation centers of patients' lymph nodes. Stimulation of TNF receptor-1 with TNF-α enhanced nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activity and viability of chronic lymphocytic leukemia cells, which was inhibited by wogonin. The therapeutic effects of wogonin were analyzed in mice after adoptive transfer of Eμ-T-cell leukemia 1 (TCL1) leukemic cells. Wogonin treatment prevented leukemia development when given early after transplantation. The treatment of full-blown leukemia resulted in the loss of the TNF receptor-1 on chronic lymphocytic leukemia cells and their mobilization to blood. Targeting TNF receptor-1 signaling is therefore proposed for the treatment of chronic lymphocytic leukemia.
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000132709 7001_ $$0P:(DE-He78)1c2351213e0199e6bd4efaceac511917$$aHanna, Bola$$b1$$udkfz
000132709 7001_ $$0P:(DE-He78)a0494aed1057846ea6c9bc93cacbe8e2$$aSchulz, Angela$$b2$$udkfz
000132709 7001_ $$0P:(DE-HGF)0$$aLucas, Fabienne$$b3
000132709 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b4
000132709 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b5$$udkfz
000132709 7001_ $$aClear, Andrew$$b6
000132709 7001_ $$0P:(DE-He78)5ad7de84a84805746cf4d7f7f90cdbff$$aOhl, Sibylle$$b7$$udkfz
000132709 7001_ $$0P:(DE-He78)c3e32dca3eea6c46d4d140757aaf6e18$$aÖztürk, Selcen$$b8$$udkfz
000132709 7001_ $$0P:(DE-He78)f3d5f16b49eb47520def635be98d5576$$aZenz, Thorsten$$b9$$udkfz
000132709 7001_ $$aStilgenbauer, Stephan$$b10
000132709 7001_ $$0P:(DE-He78)a77cbc2e7eb2157c4c0fba6159a941ec$$aLi-Weber, Min$$b11$$udkfz
000132709 7001_ $$0P:(DE-He78)92492c6eae05ee58973fc142c9201e3d$$aKrammer, Peter$$b12$$udkfz
000132709 7001_ $$aGribben, John G$$b13
000132709 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b14$$udkfz
000132709 7001_ $$0P:(DE-He78)e67f907703fcb2cf909f4d72d50268b5$$aSeiffert, Martina$$b15$$eLast author$$udkfz
000132709 773__ $$0PERI:(DE-600)2805244-4$$a10.3324/haematol.2017.177808$$gVol. 103, no. 4, p. 688 - 697$$n4$$p688 - 697$$tHaematologica$$v103$$x1592-8721$$y2018
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