Journal
BLOOD REVIEWS
Volume 27, Issue 6, Pages 261-267Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2013.08.002
Keywords
Myeloma bone disease; DKK1; Antibody; Proteasome inhibitor; Vaccine
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Funding
- National Natural Science Foundation of China [81172257]
- Xi'an Fundamental Research Funds of China [HM1117-4]
- National Cancer Institute [RO1-CA90853]
- National Institutes of Health through the University of Texas MD Anderson Cancer Center Support Grant [CA016672]
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Myeloma bone disease (MBD) is the most visible aspect of plasma cell myeloma (PCM), which is characterized by the displacement of hematopoiesis and the formation of osteolytic bone lesions. The secreted glycoprotein Dickkopf-1 (DKK1), an inhibitor of the Wnt signaling pathway, is broadly expressed in myeloma cells but highly restricted in normal tissues. DKK1 plays a critical role in several aspects of bone biology and actively participates in regulating MBD by inhibiting osteoblasts and by activating osteoclasts. Based on these findings, ongoing research has been targeting DKK1 to find novel therapeutic strategies for MBD, such as DIM-neutralizing antibodies, proteasome inhibitors, and vaccines. All these strategies have produced encouraging clinical results and consequently, revealed the significance of DKK1 in MBD. This review discusses the recent advances in our understanding of the DIM pathway signaling and how DIM can be exploited in the therapeutic intervention of MBD. Published by Elsevier Ltd.
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