Normal and oncogenic FLT3.
FLT3, a member of the class III receptor tyrosine kinases (RTKs), is preferentially expressed on the cell surface of hematopoietic progenitors, and the ligand of FLT3 (FL) is expressed as a membrane-bound or soluble form by bone marrow stroma cells. It has been disclosed that FL-FLT3 interaction plays an important role in the maintenance, proliferation and differentiation of hematopoiesis. FLT3 is also expressed in a high proportion of acute myeloid leukemia (AML) and B-lineage acute lymphoblastic leukemia cells. Activating mutations of FLT3 are the most frequent genetic lesions in AML, and AML patients with FLT3 mutations have a worse prognosis than those with normal FLT3. Exploring the mechanism by which FLT3 mutations cause autoactivation and uncontrolled signaling might lead to a better understanding of how FLT3 becomes oncogenic and provide insights for the development of new drugs.
Naoe
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Department of Hematology, Nagoya University, Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. tnaoe@med.nagoya-u.ac.jp
Kiyoi
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D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism*; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells; D014162:Transfection; D051941:fms-Like Tyrosine Kinase 3
D008024:Ligands; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3