Journal
BLOOD
Volume 117, Issue 5, Pages 1641-1651Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-09-308171
Keywords
-
Categories
Funding
- National Institutes of Health [DK071780, R020152]
- Louisiana Gene Therapy Research Consortium
- Scott and White Hospital, Texas A&M Health Science Center
Ask authors/readers for more resources
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-3 beta (GSK3 beta) causes accelerated Wnt signaling and enhanced osteogenesis in mesenchymal stem/progenitor cells, irrespective of the extracellular concentration of Wnt inhibitors. Our primary goal of this study was to evaluate a GSK3 beta inhibitor (6-bromoindirubin-3'-oxime BIO) for amelioration of bone destruction in a murine model of MBD. When measured using histomorphometry, peritumoral BIO administration improved bone quality at the bone-tumor interface and, surprisingly, increased histologically apparent tumor necrosis. Furthermore, in vitro assays demonstrated a proapoptotic effect on numerous MM cell lines. These preliminary data suggest that pharmaceutical GSK3 beta inhibition may improve bone quality in myeloma and other malignant bone diseases. (Blood. 2011; 117(5): 1641-1651)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available