In vitro growth of human multiple myeloma: Implications for biology and therapy

In vitro data present a plausible scenario for the in vivo growth of human multiple myeloma that involves interaction between the monoclonal B-cell clone and the bone marrow (BM) microenvironment. A large series of adhesion and extracellular matrix molecules trap circulating plasma cell precursors within the BM, and a battery of locally released cytokines promote the growth and final differentiation of the B-cell clone. The cytokines released by malignant plasma cells recruit and activate BM stromal cells and T lymphocytes to produce other cytokines that can act in concert in a self- perpetuating mechanism of mutual help and recruitment that favors the progressive expansion of the malignant clone through an 'avalanche' effect. Further, most cytokines produced by malignant plasma cells, stromal cells, and activated T lymphocytes have osteoclast-activating properties, thus explaining why the expansion of the B-cell clone is matched by the activation and numerical increase of osteoclasts.