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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-02-0492.
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Blood, 1 September 2002, Vol. 100, No. 5, pp. 1532-1542
REVIEW ARTICLE
The roles of FLT3 in hematopoiesis and leukemia
D. Gary Gilliland and
James
D. Griffin
From the Brigham and Women's Hospital, Howard Hughes
Medical Institute, Harvard Medical School and the Dana-Farber Cancer
Institute, Harvard Medical School, Boston, MA.
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.
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