Pharmaceutical inhibition of glycogen synthetase kinase-3β reduces multiple myeloma-induced bone disease in a novel murine plasmacytoma xenograft model.

ABSTRACT: Multiple myeloma (MM) is a malignancy of plasma cells that accumulate in the bone marrow. MM is incurable with approximately 100 000 patients currently in the United States and 20 000 new cases diagnosed yearly. The malignancy causes displacement of hematopoiesis and formation of osteolytic bone lesions also known as myeloma bone disease (MBD). At diagnosis, 79% of patients suffer from MBD associated with severe pain and increased mortality. Wnt inhibitors secreted by MM cells inhibit osteogenesis and promote osteoclastogenesis, therefore rapid targeting of Wnt inhibitors is necessary to prevent potentially irreversible effects on the stroma, which could lead to incurable MBD. Inhibition of glycogen synthetase kinase-3β (GSK3β) causes accelerated Wnt signaling and enhanced osteogenesis in

SUBMITTER: Gunn WG 

PROVIDER: S-EPMC3318776 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature