THE FLT3 LIGAND IS A DIRECT AND POTENT STIMULATOR OF THE GROWTH OF PRIMITIVE AND COMMITTED HUMAN CD34(-MARROW PROGENITOR CELLS IN-VITRO() BONE)

The present studies investigated the effects of the recently cloned fl t3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34(+) bone marrow (BM) progenitor ce lls. FL alone was a weak growth stimulator of CD34(+) BM cells. but sy nergistically and directly enhanced colony formation in combination wi th 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 progenitor s 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 presenc e of serum, a low number of BFU-E colonies were formed in response to FL plus erythropoietin (Epo) under serum-deprived conditions. In addit ion. FL both in serum-containing and serum-deprived cultures stimulate d colony formation of more committed myeloid progenitors in CD34(+)CD7 1(+) BM cells. Thus. FL potently stimulates the growth of primitive an d more committed human BM progenitor cells. (C) 1996 by The American S ociety of Hematology.