title: Developing target therapy against oncogenic tyrosine kinase in myeloid maliganacies.
abstract: Myeloid malignancies are frequently associated with translocations and mutations of tyrosine kinase genes. Fusion genes involving ABL, ARG, PDGFRs, JAK2, SYK, TRKC, and FGFRs, and gain-of-function mutations of FLT3, KIT and JAK2 have been detected at various rates in myeloproliferative disease and acute myeloid leukemia. Furthermore, abnormal overexpression of tyrosine kinases such as FLT3 has also been reported. These gene products are constitutively activated and potentially transform hematopoietic cells by augmentation of proliferation and enhanced viability. Since the fusion or mutation of tyrosine kinase is a primary and central event in chronic myeloproliferative diseases, targeting the kinase activity has been thought to be an ideal intervention to treat these diseases. The clinical success of imatinib for chronic myeloid leukemia has made this idea a reality, and has accelerated the development of new tyrosine kinase inhibitors (TKIs). Challenging studies with TKIs have also been reported for acute myeloid leukemia. This review will focus on recent trials of TKIs against oncogenic tyrosine kinases (ABL, PDGFRs, FLT3 and KIT) in myeloid malignancies.
authors.affiliation: Department of Hematology & Oncology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan. tnaoe@med.nagoya-u.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases