Targeting the BAFF/APRIL cytokine network in multiple myeloma

The BAFF/APRIL cytokine network is intimately linked through three different receptors to the survival and fi tness of B lineage cells, from the first expression of a complete B cell receptor to their differentiation to memory B and plasma cells. The speci fi c, pervasive, and survival-linked nature of the relationship between B lineage cells and this cytokine network make it both a likely disease modi fi er and a tantalizing target for therapeutic intervention in humoral immune pathologies. Some current therapeutics directly targeting the BAFF/APRIL cytokine network have been developed and undergone clinical trials in the context of autoimmunity with some limited success. Despite a powerful rationale and a constantly deepening mechanistic understanding of the BAFF/APRIL cytokine network in normal and malignant plasma cells, trials of cytokine network-targeted therapeutics in multiple myeloma are still in their infancy and have shown only minor promise. There is signi fi cantly greater potential in inhibiting NF-kB, a downstream mediator of BAFF/APRIL signals.