PROLIFERATION AND DIFFERENTIATION OF MYELODYSPLASTIC CD34(-FREE MEDIUM .2. RESPONSE TO COMBINED COLONY-STIMULATING FACTORS() CELLS IN SERUM)

To investigate the role of colony stimulating factors (CSFs) in the pr oliferation and differentiation of progenitor cells from myelodysplast ic syndromes (MDS), marrow progenitor cells from 18 MDS patients were highly purified using CD34 monoclonal antibody and immunomagnetic micr ospheres (MDS CD34(+) cells). These cells were cultured in serum-free medium with various combinations of five colony stimulating factors (C SFs): recombinant human interleukin-3 (rIL-3), granulocyte/macrophage- CSF (rGM-CSF), granulocyte-CSF (rG-CSF), macrophage-CSF (rM-CSF), and erythropoietin (rEP). Among the tested CSFs, such as rM-CSF, rG-CSF, r GM-CSF and rIL-3, a combination of the first three CSFs was the most e ffective stimulus for the proliferation of non-erythroid MDS progenito r cells. An increase of undifferentiated ''blast'' cell colonies in 5/ 18 MDS patients occurred and these 5 patients belonged to the high-ris k group. In the presence of these three CSFs, rIL-3 had no effect on t he proliferation and differentiation of MDS CD34(+) cells; however, IL -3 was efficient for the proliferation of MDS CD34(+) cells to the ery throid lineage. rGM-CSF or rIL-3 alone did not efficiently support pro liferation and differentiation of CD34(+) cells. M-CSF is present in n ormal human serum at a concentration of 550 +/- 110 U/ml, a concentrat ion exceeding that used in this study (100 U/ml). Therefore, in vivo a dministration of G-CSF combined with GM-CSF to MDS patients may be one of the most effective CSF combinations for proliferation of MDS proge nitor cells to the non-erythroid lineage. However, the effect on the c apacity for differentiation was minimal, especially in patients belong ing to the high-risk group.