Multiple myeloma is an incurable cancer that results from the accumulation of several genetic mutations. These mutations uniquely distinguish the cancer cells from normal cells, and it is believed that tumor cells become addicted to the pathways activated by these mutations. As a result they represent a tumor specific vulnerability that can be exploited therapeutically using drugs that target the pathways activated by mutation. We have recently identified mutations in myeloma cells that activate one of the most fundamental pathways in immunology, called the NFkB pathway. We now propose to study the functional consequence of these mutations.