Blys/Br3 Receptor Signaling In The Biology And Pathophysiology Of Aggressive B-Cell Lymphomas

Lymphoid neoplasms usually display various genetic alterations that dysregulate normal immune functions, primarily through abnormal cellular growth and survival mechanisms that expand and immortalize a single neoplastic clone, to the detriment of the indigenous normal immune system, and eventually the host. In addition to the nonrandom genetic translocations, other important cellular abnormalities are also involved. The abnormalities in cellular regulation generally occur in one or more of the following four areas: cell death, cell cycle progression, NF-kappa B activation, or critical signal transduction pathways, usually from cell surface growth and survival receptors. Recent studies of BLyS/BAFF family members, BLyS and APRIL, have shown their importance in non-Hodgkin's B-cell lymphoma (NHL-B), chronic lymphoid leukemia (CLL), and plasma cell myeloma cell growth and survival. In this chapter, we will discuss how BLyS is involved in mechanisms of tumor cell proliferation and survival in these malignant lymphoid cells. Potential therapeutic approaches to these lymphoid malignances through inhibition of BLyS signaling pathways are also discussed.