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FLT3 receptor expression on the surface of normal and malignant human
hematopoietic cells
AM Turner, NL Lin, S Issarachai, SD Lyman and VC Broudy
Division of Hematology, University of Washington, Seattle 98195, USA.
FLT3 ligand is a hematopoietic growth factor that plays a key role in
growth of primitive hematopoietic cells. FLT3 receptor mRNA is found in
early hematopoietic progenitors and in human myeloid leukemia blasts. Much
less is known about the surface expression of FLT3 receptor on human
hematopoietic cells. Using human 125I-FLT3 ligand, we have identified and
characterized surface FLT3 receptors on normal and malignant human
hematopoietic cells and cell lines. Our results showed that surface display
of FLT3 receptor was greatest in fresh myeloid leukemia blast cells and
myeloid leukemia cell lines. Erythroleukemic and megakaryocytic leukemia
cell lines (n = 5) bound little to no 125I- FLT3 ligand. Scatchard analysis
of 125I-FLT3 ligand binding data shows that three myeloid leukemia cell
lines, ML-1, AML-193, and HL-60, as well as normal human marrow mononuclear
cells, exhibit high affinity FLT3 receptors. Crosslinking of 125I-FLT3
ligand to FLT3 receptors on the surface of ML-1 myeloid leukemia cells
indicates that the FLT3 ligand. The rates of FLT3 ligand internalization
and degradation were determined by binding 125I-FLT3 ligand to ML-1 cells
and acid stripping to distinguish surface bound from internalized ligand.
Internalized 125I-FLT3 ligand was detected within 5 minutes after binding
to ML-1 cells. In addition, we evaluated the effect of FLT3 ligand on
megakaryocytic colony growth and nuclear endoreduplication, alone or in the
presence of thrombopoietin. FLT3 ligand did not promote colony forming unit
megakaryocyte (CFU-Meg) colony growth or megakaryocyte nuclear maturation,
nor did FLT3 ligand augment the effects of thrombopoietin on these measures
of megakaryopoiesis. These data indicate that the FLT3 receptor shares
several characteristics with the c-kit receptor including dimerization and
rapid internalization. However, the more restricted cellular distribution
of the FLT3 receptor may target the effects of FLT3 ligand to primitive
hematopoietic cells and to myeloid and lymphoid progenitor cells, in
contrast to the pleiotropic effects of the c-kit receptor ligand, stem cell
factor.
Volume 88,
Issue 9,
pp. 3383-3390,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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