Multiple Myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of terminally differentiated, antibody-producing plasma cells in the bone marrow. Though the therapy of MM has evolved over the past decade, glucocorticoids remain the most effective agents for the treatment of this disease. Glucocorticoid induced cytotoxicity requires an intact functional glucocorticoid receptor alpha (GRa). Two splice variants (GR-P and GRB) have been described that can modulate glucocorticoid mediated apoptosis. In addition, absent or diminished expression of GRa is associated with resistance to steroid therapy. There has not been a systematic analysis addressing the prognostic significance of GR expression in MM. In contrast, estrogen and progesterone receptor expression in breast cancer has had a profound impact on prognostication and determination of the treatment of this tumor. ECOG trial E1A00 randomizes newly diagnosed MM patients to Thalidomide plus Dexamethasone versus Dexamethasone alone. Pre-treatment marrow specimens are available to assess GR expression in MM and to correlate the pattern of expression with well characterized prognostic factors (i.e. cytogenetics, beta 2 microglobulin, C-reactive protein, LDH, plasma cell labeling index, creatinine, hemoglobin, and serum albumin), response to steroid therapy and duration of response. Post-treatment samples are also available from a significant number of patients that will allow an assessment of Dexamethasone Thalidomide impact on GR expression. Data obtained from this project has the potential to help refine the use of steroids in the treatment of MM and will have significant implications for related hematologic diseases.
