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The FLT3 ligand is a direct and potent stimulator of the growth of
primitive and committed human CD34+ bone marrow progenitor cells in vitro
LS Rusten, SD Lyman, OP Veiby and SE Jacobsen
Department of Immunology, Norwegian Radium Hospital, Oslo, Norway.
The present studies investigated the effects of the recently cloned flt3
ligand (FL) on the in vitro growth and differentiation of primitive and
committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL
alone was a weak growth stimulator of CD34+ BM cells, but synergistically
and directly enhanced colony formation in combination with interleukin (IL)
3, granulocyte colony-stimulating factor (G-CSF), CSF-1, granulocyte
macrophage (GM) CSF stem cell factor (SCF), and IL-6. FL and SCF were
equally effective in stimulating colony formation in combination with IL-3.
However, the tri-factor combination of FL + IL-3 + SCF stimulated 2.3-fold
and 2.5-fold more colonies than FL + IL-3 and SCF + IL-3, respectively.
These additional recruited progenitors appeared to be predominantly located
in a primitive (CD71-) subset of the CD34+ progenitors, as 4.5-fold more
colonies were formed by CD34+CD71- cells in response to FL + IL-3 + SCF
than to FL + IL-3 or SCF + IL-3. Similar findings were observed in
serum-containing and serum-deprived cultures. Whereas FL did not enhance
burst-forming unit-erythroid (BFU-E) colony formation of CD34+ BM cells in
the presence of serum, a low number of BFU-E colonies were formed in
response to FL plus erythropoietin (Epo) under serum-deprived conditions.
In addition, FL both in serum-containing and serum-deprived cultures
stimulated colony formation of more committed myeloid progenitors in
CD34+CD71+ BM cells. Thus, FL potently stimulates the growth of primitive
and more committed human BM progenitor cells.
Volume 87,
Issue 4,
pp. 1317-1325,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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