Role of physiologic concentrations of stem cell factor in leukemic type growth of myelodysplastic CD34(+) cells

The stem cell factor (SCF: a ligand for c-kit) plays a central role in the growth of myelodysplastic (MDS) progenitor cells with leukemic type growth. In this study, the role of physiologic concentrations of SCF on the prolif eration and differentiation on MDS progenitor cells was further analyzed in the presence of combined cytokines. For this purpose, marrow CD34(+) cells were purified up to 94% for 12 normal individuals and 90% for 18 MDS patie nts, using monoclonal antibodies and immunomagnetic microspheres. The purif ied CD34+ cells were cultured for 14 days with saturating doses of cytokine s, including recombinant human macrophage colony stimulating factor (rM-CSF ), granulocyte-CSF (rG-CSF), granulocyte/macrophage-CSF (rGM-CSF), interleu kin-3 (rIL-3) and rSCF. The clonal growth of MDS CD34(+) cells supported by a combination of all the above cytokines was then subdivided into the two patterns of leukemic or non-leukemic. The role of various concentrations of rSCF (0, 0.5, 5, 50 and 500 ng ml(-1)), with or without the above cytokine s, in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. The physiologic concentration of SCF at 5 ng ml(-1) significant ly increased undifferentiated 'blast cell' colonies or clusters in leukemic type growth of MDS CD34+ cells over that seen in normal CD34+ cells. SCF i s present in plasma at a level of ng ml(-1). This means that progenitor cel ls are continuously exposed to stimulation by SCF in vivo and that MDS leuk emic cells have a growth advantage over normal blasts. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.