title: The B-cell receptor pathway: a critical component of healthy and malignant immune biology.
abstract: The pathogenesis and progression of normal B-cell development to malignant transformation of chronic lymphocytic leukemia (CLL) is still poorly understood and has hampered attempts to develop targeted therapeutics for this disease. The dependence of CLL cells on B-cell receptor signaling has fostered a new area of basic and therapeutic research interest. In particular, identification of the dependence of CLL cells on both phosphatidylinositol 3-kinase delta and Bruton's tyrosine kinase signaling for survival and proliferation has come forth through well-performed preclinical studies and subsequent trials demonstrating dramatic efficacy. This review outlines essential components of B-cell receptor signaling and briefly addresses therapeutics that are emerging to target these in patients with CLL and related lymphoid malignancies.
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH. Electronic address: jason.dubovsky@osumc.edu.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Dubovsky
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6