Abstract
The antigen-dependent B-cell receptor (BCR) is triggered by binding to external antigens and transmits signals in normal B lymphocytes. Tonic signaling through the BCR plays a crucial role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). Spleen tyrosine kinase (Syk) is a key component of both BCR signals, and regulates multiple physiological functions of B lymphocytes. Studies have defined enhanced gene expression and protein expression of Syk in CLL cells which are closely related to the status of the immunoglobulin heavy chain variable region genes (IgVH). Recently, abrogating the BCR-induced signaling pathway by Syk inhibitors has represented a novel and active therapeutic approach for CLL. Studies of the correlation between Syk and ZAP-70 expression in CLL cells have brought a new perspective to determining the value of Syk in evaluating the effect of therapy and the prognosis of CLL. Therefore, we here review the role of Syk in the pathogenesis of CLL and provide an update of progress in the clinical development of Syk inhibitors.
Keywords:
Syk; Syk inhibitors; ZAP-70; chronic lymphocytic leukemia.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Gene Expression Regulation, Leukemic
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Humans
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
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Leukemia, Lymphocytic, Chronic, B-Cell / etiology*
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
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Molecular Targeted Therapy
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, B-Cell / metabolism
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Signal Transduction / drug effects
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Syk Kinase
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ZAP-70 Protein-Tyrosine Kinase / genetics
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Antineoplastic Agents
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Intracellular Signaling Peptides and Proteins
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Protein Kinase Inhibitors
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Receptors, Antigen, B-Cell
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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ZAP-70 Protein-Tyrosine Kinase