The classical pathway of nuclear factor-kappa B (NF-κB) has been well studied in myeloma. Recently, an alternative pathway of NF-κB activation was described which plays an important role in the development of immune system. This alternate NF-κB pathway has not been studied in multiple myeloma. The goals of this proposal are to study the contribution of the alternate NF-κB pathway to the development of multiple myeloma. This research will provide a better understanding of the role of the alternative NF-κB pathway in myeloma and provide novel molecularly targeted strategies for its treatment.