MOLECULAR AND BIOLOGICAL FUNCTION OF CD40 IN MYELOMA

DESCRIPTION (Adapted from the Investigator's Abstract): Multiple myeloma is a universally fatal disease characterized by the accumulation of malignant plasma cells in the bone marrow. Because of the ability of IL-6 to drive myeloma cell proliferation, the investigator's previous studies focused on the molecular changes that result in deregulation of tumor cell IL-6 expression. The study proposed in this application is based on two hypotheses, 1) that overexpression of the IGF-I receptor is a crucial component of the altered IL-6 responsiveness of myeloma cells; 2) that IL-6 stimulates myeloma cell IGF and IGF-I-R expression, thereby further potentiating tumor cell growth. To test these hypotheses, the investigator will 1) determine the mechanism by which anti-IGF-I-R mABs inhibit IL-6-stimulated myeloma cell proliferation; 2) determine the role of IGF-I receptor expression in IL-6-mediated myeloma cell growth; and 3) determine the mechanism(s) underlying overexpression of the IGF-I receptor in myeloma cells. Information obtained from these studies has the potential to provide important insight into the genetic events that occur during tumor progression in myeloma patients, and also may facilitate determination of which patients are in need or more aggressive therapy.