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Protein Kinase C-beta-Dependent Activation of NF-kappa B in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons78648

Schmidt-Supprian,  Marc
Schmidt-Supprian, Marc / Molecular Immunology and Signaltransduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Lutzny, G., Kocher, T., Schmidt-Supprian, M., Rudelius, M., Klein-Hitpass, L., Finch, A. J., et al. (2013). Protein Kinase C-beta-Dependent Activation of NF-kappa B in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo. CANCER CELL, 23(1), 77-92. doi:10.1016/j.ccr.2012.12.003.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-000E-B247-8
Zusammenfassung
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironrnent. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-beta II and the subsequent activation of NF-kappa B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-beta knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-beta II-NF-kappa B signaling pathway in the tumor microenvironment. Upregulated stromal PKG-beta II in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies.