The roles of FLT3 in hematopoiesis and leukemia

FLT3 is a receptor tyrosine kinase expressed by immature hematopoietic cells and is important for the normal development of stem cells and the immune system. The ligand for FLT3 is expressed by marrow stromal cells and other cells and synergizes with other growth factors to stimulate proliferation o...

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Bibliographic Details
Published in:Blood 2002-09, Vol.100 (5), p.1532-1542
Main Authors: Gilliland, D. Gary, Griffin, James D.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
fms-Like Tyrosine Kinase 3
Hematologic and hematopoietic diseases
Hematopoiesis - physiology
Humans
Leukemia - metabolism
Leukemia - physiopathology
Leukemia, Experimental - metabolism
Leukemia, Experimental - physiopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Mutation
Proto-Oncogene Proteins - physiology
Receptor Protein-Tyrosine Kinases - physiology
Receptors, Cell Surface - physiology
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Summary:FLT3 is a receptor tyrosine kinase expressed by immature hematopoietic cells and is important for the normal development of stem cells and the immune system. The ligand for FLT3 is expressed by marrow stromal cells and other cells and synergizes with other growth factors to stimulate proliferation of stem cells, progenitor cells, dendritic cells, and natural killer cells. Mutations of FLT3 have been detected in about 30% of patients with acute myelogenous leukemia and a small number of patients with acute lymphocytic leukemia or myelodysplastic syndrome. Patients with FLT3 mutations tend to have a poor prognosis. The mutations most often involve small tandem duplications of amino acids within the juxtamembrane domain of the receptor and result in constitutive tyrosine kinase activity. Expression of a mutant FLT3 receptor in murine marrow cells results in a lethal myeloproliferative syndrome and preliminary studies suggest that mutant FLT3 cooperates with other leukemia oncogenes to confer a more aggressive phenotype. Taken together, these results suggest that FLT3 is an attractive therapeutic target for kinase inhibitors or other approaches for patients with mutations of this gene.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2002-02-0492