Spleen tyrosine kinase as a molecular target for treatment of leukemias and lymphomas.
Spleen tyrosine kinase (SYK) has emerged as a potential molecular target for the treatment of B-lineage leukemias and lymphomas. Here, we provide an overview of the current state of knowledge regarding the regulatory signaling function of SYK and its role in the pathogenesis of B-lineage lymphoid malignancies, available methods and drug candidates for targeting SYK, as well as compelling preclinical and clinical evidence regarding the clinical potential of inhibiting SYK. The further development of rationally designed SYK inhibitors may provide the foundation for therapeutic innovation against B-lineage leukemias and lymphomas.
Uckun
Fatih M
FM
Developmental Therapeutics Program, Institute for Pediatric Clinical Research, Children's Hospital Los Angeles, MS#57, Los Angeles, CA 90027, USA. fmuckun@chla.usc.edu
Qazi
Sanjive
S
D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase
D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase