title: The biological rationale and clinical efficacy of inhibition of signaling kinases in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is still incurable, with considerable resistance to the standard therapy. CLL cells receive anti-apoptotic and pro-proliferation stimuli in lymph nodes and bone marrow, mainly through B cell receptor activation and TNF-receptor family ligation. In recent years, the focus for finding new drugs has shifted to blocking signals from the microenvironment. Novel therapeutical agents interfere with these microenvironmental interactions, and include inhibitors of kinases Syk, Btk and PI3Kδ. In this review we will focus on the microenvironmental interactions of CLL and the role of tyrosine kinases. Furthermore, early results from clinical trials with kinase inhibitors are discussed.
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: de Weerdt
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Marinus H
authors.initials: MH
authors.lastname: van Oers
authors.forename: Arnon P
authors.initials: AP
authors.lastname: Kater
mesh_terms: D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases