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
- Lutzny, G.
- Kocher, T.
- Schmidt-Supprian, M.
- Rudelius, M.
- Klein-Hitpass, L.
- Finch, A.
- Duerig, J.
- Wagner, M.
- Haferlach, C.
- Kohlmann, A.
- Schnittger, S.
- Seifert, M.
- Wanninger, S.
- Zaborsky, N.
- Oostendorp, R.
- Ruland, J.
- Leitges, M.
- Kuhnt, T.
- Schaefer, Y.
- Lampl, B.
- Peschel, C.
- Egle, A.
- Ringshausen, I.
DOIAbstract
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 lymp...
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