BoneKEy Reports | BoneKEy Watch
GDF15 and AXII could be therapeutic targets in multiple myeloma
DOI:10.1038/bonekey.2012.74
Bone marrow mesenchymal stem cells from patients with multiple myeloma (MM) overexpress growth differentiation factor 15 (GDF15); Corre et al. show that GDF15 is able to boost the survival of MM cells, including primary MM cells, within the stroma of the bone marrow. MM cells that overexpress GDF15 show resistance to several therapeutic agents, including melphalan and bortezomib. GDF15 seems to act through the AKT signaling pathway, but not through the Src or ERK1/2 pathways, and is a predictor of significantly lower overall survival.
Previous research had also suggested that annexin II (AXII) and its receptor were important in MM. AXII is expressed at high levels in primary MM cells, stromal cells, osteoblasts and osteoclasts, all of which help to sustain MM cell growth. D'Souza et al. used a variety of methods to demonstrate that the receptor for AXII is expressed by MM cell lines and also by CD138+ cells derived from patients with MM. AXII and and its receptor mediate the interaction between osteoblasts, stromal cells and MM cells, stimulating the growth of MM cells via the ERK1/2 pathway in marrow stromal cells and the AKT pathway in MM cells.
Editor's comment: These two studies increase our understanding of multiple myeloma, identifying GDF15 and annexin II as factors that play a key role in promoting the survival and growth of MM cells in the bone microenvironment. Both could be potential novel therapeutic targets for this currently incurable hematological malignancy.
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