title: Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications.
abstract: FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene, and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3, leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation, with a particular focus on the effects on transcription factors. Moreover, this review describes novel FLT3-targeted therapies, as well as efficient combination therapies for FLT3-mutated leukemia cells.
authors: The Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0373, Japan. shin@kitasato-u.ac.jp
authors: Shinichiro
authors: S
authors: Takahashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014157:Transcription Factors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3