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Title:

Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance.

Document type:
Article; Journal Article; Research Support, Non-U.S. Gov't
Author(s):
Park, Eugene; Chen, Jingyu; Moore, Andrew; Mangolini, Maurizio; Santoro, Antonella; Boyd, Joseph R; Schjerven, Hilde; Ecker, Veronika; Buchner, Maike; Williamson, James C; Lehner, Paul J; Gasparoli, Luca; Williams, Owen; Bloehdorn, Johannes; Stilgenbauer, Stephan; Leitges, Michael; Egle, Alexander; Schmidt-Supprian, Marc; Frietze, Seth; Ringshausen, Ingo
Abstract:
Overcoming drug resistance remains a key challenge to cure patients with acute and chronic B cell malignancies. Here, we describe a stromal cell-autonomous signaling pathway, which contributes to drug resistance of malignant B cells. We show that protein kinase C (PKC)-β-dependent signals from bone marrow-derived stromal cells markedly decrease the efficacy of cytotoxic therapies. Conversely, small-molecule PKC-β inhibitors antagonize prosurvival signals from stromal cells and sensitize tumor ce...     »
Journal title abbreviation:
Sci Transl Med
Year:
2020
Journal volume:
12
Journal issue:
526
Fulltext / DOI:
doi:10.1126/scitranslmed.aax9340
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/31941829
Print-ISSN:
1946-6234
TUM Institution:
Experimentelle Hämatologie (Prof. Schmidt-Supprian); Institut für Klinische Chemie und Pathobiochemie
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