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

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. 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)-?II and the subsequent activation of NF-?B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-? knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-?II-NF-?B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-?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.     «

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. 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)-?II and the subsequent activation of NF-?B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-? knockout mice are insusceptible to CLL transplantations...     »