Journal Article

DKFZ-2018-00363

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic leukemia that can be therapeutically targeted by the flavonoid wogonin.

Dürr, C. (First author)DKFZ* ; Hanna, B.DKFZ* ; Schulz, A.DKFZ* ; Lucas, F.DKFZ* ; Zucknick, M.DKFZ* ; Benner, A.DKFZ* ; Clear, A. ; Ohl, S.DKFZ* ; Öztürk, S.DKFZ* ; Zenz, T.DKFZ* ; Stilgenbauer, S. ; Li-Weber, M.DKFZ* ; Krammer, P.DKFZ* ; Gribben, J. G. ; Lichter, P.DKFZ* ; Seiffert, M. (Last author)DKFZ*

2018
Ferrata Storti Foundation Pavia

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Please use a persistent id in citations: doi:10.3324/haematol.2017.177808

Abstract: 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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Contributing Institute(s):

1. Molekulare Genetik (B060)
2. Biostatistik (C060)
3. Translationale Onkologie (G100)
4. Immungenetik (D030)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2018

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DOAJ Seal ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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