Gfi1: a new therapeutic target for multiple myeloma bone disease
Inhibition of osteoblast differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. The authors of this study [1] developed a murine multiple myeloma model in which the bone marrow stromal cells remained unresponsive to osteoblast differentiation, inhibiting signals after removal of MM cells.
They found that bone marrow stromal cells, in MM-bearing mice and in MM patients, had an increased expression of the transcriptional repressor Gfi1. This factor repressed the transcription factor Runx2 which is critical for osteoblast differentiation. Increased Gfi1 level and Runx2 repression were blocked by anti-TNF-α and IL-7 antibodies. These cytokines are produced massively by MM cells. Importantly, bone marrow stromal cells isolated from Gfi1-/- mice were resistant to MM-induced osteoblastogenesis suppression. Furthermore, Gfi1 knockdown by specific siRNA in bone marrow stromal cells from MM patients restored Runx2 level and osteoblastogenesis markers.
These data highlight the important role of Gfi1 cellular amount in prolonged MM-induced osteoblast suppression and identifies Gfi1 as a new potential therapeutic target for MM bone disease.
- D’Souza S et al. Blood. 2011; doi:10.1182/blood-2011-04-346775.
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