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Bone marrow stromal cells influence myeloma progression via Dkk1


Multiple myeloma progression depends on numerous factors but it has proved difficult to study the interactions between cells in the bone microenvironment and how they influence the course of the disease. In order to investigate the possible contribution made by bone marrow stromal cells (BMSCs), Fowler et al. have designed a series of experiments using a mouse model of multiple myeloma.

Mice were inoculated either with 5TGM1-GFP myeloma cells alone, with myeloma cells plus BMSCs that had been derived from mice with active myeloma, or with BMSCs alone. In the first group, none of the mice developed myeloma. Those in the second group did, developing tumors within the bone marrow as well as exhibiting osteolytic bone disease. Inoculation with BMSCs only resulted in strong osteoblast suppression, something known to be associated with increased levels of the Wnt signaling inhibitor, Dkk1.

The researchers noted a high level of Dkk1 gene expression in the BMSCs, so prepared Dkk1-knockout BMSCs and inoculated them into the mouse model; in these mice, myeloma progression was much slower and osteolytic bone disease was less apparent.

Editor's comment: These results reveal the importance of bone marrow stromal cells in the early stages of myeloma development and provide further evidence that Dkk1 is a promising therapeutic target.

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