Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation-inducing ligand in hematologic malignancies.
B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), members of the tumor necrosis family of ligands, are expressed by monocytes, macrophages, and dendritic cells, and increased expression of these ligands is noted in lymphomas and plasma cell malignancies. BLyS and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell maturation, transmembrane activator and calcium-modulating cyclophilin ligand interactor, or BAFF-R have been reported in various B-cell malignancies, including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS (in the tumor and in the serum) increased with the transformation of the tumors to a more aggressive phenotype. A high BLyS level inversely correlated with a poor median overall survival, presence of constitutional symptoms, and increased levels of lactate dehydrogenase in patients with non-Hodgkin's lymphoma. Additionally, patients who responded to therapy had a lower BLyS level than those with progressive disease. Several agents targeting BLyS and APRIL are currently being pursued in phase I clinical studies in patients with B-cell malignancies.
Shivakumar
Latha
L
CIG Media Group, LP, Dallas, TX, USA.
Ansell
Stephen
S
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002986:Clinical Trials as Topic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13