In multiple myeloma, malignant plasma cells spread in the bone marrow, compromising hematopoiesis and creating soft lesions in the bone surface, which causes osteolytic bone disease. Jessica Fowler and colleagues made a mouse model lacking the immunoglobulin recombination enzyme, RAG-2. Inoculation of RAG-2 null mice with multiple myeloma cells causes tumor formation in the bone marrow and osteolytic bone disease, similar to human patients. This model is amenable to additional genetic modifications and deletion of another cancer-related gene, Mmp9, predictably alters the tumor microenvironment and facilitates cancer progression.

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