title: B-cell receptor signaling in chronic lymphocytic leukemia and other B-cell malignancies.
abstract: B-cell receptor (BCR) signaling has emerged as a key pathway for the expansion of neoplastic B-cell clones in several B-cell malignancies. The mechanisms that activate BCR signaling differ substantially among subtypes of B-cell lymphoma and leukemia. These include BCR stimulation by foreign or self-antigens, or the acquisition of mutations in components of the BCR pathway that result in autonomous or enhanced antigen-induced BCR signaling. Targeting BCR signaling with selective inhibitors of the BCR-associated kinases Bruton's tyrosine kinase, spleen tyrosine kinase, and phosphoinositide 3-kinase delta induces high response rates in patients with chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and diffuse large B-cell lymphoma of the activated B-cell-like subtype and is currently transforming the therapeutic landscape in these diseases. Here we review the mechanisms of BCR activation that govern growth and survival of malignant B cells. We also summarize recent clinical trials of BCR inhibitors, with a focus on the most clinically advanced agents.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koehrer
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell