FMS-Like Tyrosine Kinase 3 in Normal Hematopoiesis and Acute Myeloid Leukemia

Authors

  • Bertrand W. Parcells,

    1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
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  • Alan K. Ikeda,

    1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
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  • Tiffany Simms-Waldrip,

    1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
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  • Theodore B. Moore,

    1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
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  • Kathleen M. Sakamoto M.D., Ph.D.

    Corresponding author
    1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
    2. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
    3. Division of Biology, California Institute of Technology, Pasadena, California, USA
    • A2-412 MDCC CHS, Division of Hematology-Oncology, Mattel Children's Hospital, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, California 90095-1752, USA. Telephone: 310-794-7007; Fax: 310-206-8089
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Abstract

Ligand-mediated activation of the FMS-like tyrosine kinase 3 (FLT3) receptor is important for normal proliferation of primitive hematopoietic cells. However, activating mutations in FLT3 induce ligand-independent downstream signaling that promotes oncogenesis through pathways involved in proliferation, differentiation, and survival. FLT3 mutations are identified as the most frequent genetic abnormality in acute myeloid leukemia and are also observed in other leukemias. Multiple small-molecule inhibitors are under development to target aberrant FLT3 activity that confers a poor prognosis in patients.

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