THE EFFECT OF STEM-CELL FACTOR, INTERLEUKIN-3 AND ERYTHROPOIETIN ON IN-VITRO ERYTHROPOIESIS IN MYELODYSPLASTIC SYNDROMES

An inherent defect of erythroid differentiation at the colony-forming unit blast (CFU-blast) compartment and (or) an impaired response of ea rly erythroid progenitors (BFU-E) to growth stimulation are both consi dered to contribute to anemia in myelodysplastic syndromes (MDS). With the intention of improving survival and growth of early erythroid pro genitors we investigated the effect of stem-cell factor (SCF) and inte rleukin-3 (IL-3) alone and in combination with erythropoietin, on the in vitro erythropoiesis of 13 patients with MDS and of three normal co ntrols. SCF and IL-3 alone did not promote erythroid colony growth in MDS, while 3 cases responded to erythropoietin alone. In each of these , BFU-E colony growth could be increased by SCF, which was also found in all normal bone marrows. Altogether 6 cases showed a significant en hancement of BFU-E colony numbers by the combination of SCF and erythr opoietin as compared to erythropoietin alone (P = 0.036). Out of the 6 responding cases, 5 belonged to the FAB-classified subgroups refracto ry anemia (RA) and refractory anemia with ringed sideroblasts (RA/RS) (5/5), while 1 patient was classified as having refractory anemia with excess of blasts (RAEB) (1/4). No patient with refractory anemia with excess of blasts in transformation (RAEB-T) (0/4) responded. Tn spite of these positive effects, the absolute number of BFU-E colonies rema ined reduced in all MDS cases when compared to normal controls. IL-3 p roved ineffective in increasing the response to erythropoietin in MDS although it increased erythropoietin-induced BFU-E formation in normal controls significantly. We conclude that the striking synergistic eff ect of SCF and erythropoietin on erythroid colony formation seen with normal bone marrow is conserved in most cases with RA and RA/RS. In RA EB and RAEB-T the intrinsic defect of the erythroid differentiation pa thway cannot be overcome by SCF.