Cellular resistance mechanisms with impact on the therapy of multiple myeloma

Multiple myeloma (MM) is characterized by bone marrow infiltration with abnormal plasma cells which synthesize monoclonal immunoglobulins (Ig) or Ig fragments. Regularly, MM cells exhibit a high intrinsic resistance to available chemotherapeutic strategies. A number of cellular alterations including the cellular membrane, such as mutations of the glucocorticoid receptor or expression of membrane transport proteins, detoxification mechanisms and altered expression of topoisomerases, have been described. In addition to anti-apoptotic survival mechanisms, involving abnormalities of several oncogenes and suppressor genes (ras, c-myc, p53, Rh and bcl-2), the broad resistance spectrum might be explained but clinical studies which include the evaluation of resistance factors are missing. On the other hand, risk factor evaluation is important as a number of therapeutical strategies with different intensities from corticosteroid monotherapy up to high-dose chemotherapy with tandem autologous bone marrow transplantation exist.