Thymosin β4 in multiple myeloma: friend or foe

Multiple myeloma (MM) is a malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow(BM).Because of the known involvement of thymosin bèta 4 (Tbèta4) in metastasis of tumor cells,we examined the expression and role of Tbèta4 inMMdisease. In a large patient population, we demonstrated that Tbèta4 expression was significantly lower in myeloma cells compared to normal plasma cells and that patients with a high Tbèta4 expression had a longer event free and overall survival. The decreased Tbèta4 expression was also found in the murine 5TMM model. To study its function, we overexpressed the Tbèta4 gene in 5T33MMvt cells by lentiviral transduction. These cells demonstrated a decreased proliferative capability and an increased sensitivity to apoptosis. Mice injected with Tbèta4-overexpressing cells showed a prolonged survival compared to mice injected with controls. In contrast to its role in solid tumors, we found a decreased expression inmyeloma cells compared to their normal counterpart and studies with overexpression of the Tbèta4 gene indicated a tumor suppressive function of Tbèta4 in myeloma development.