Abstract
Erythropoiesis in response to erythropoietin (Epo) in myelodysplastic syndrome (MDS) in vitro and in vivo is severely impaired. We investigated the stimulative effect of c-kit ligand (KL) on the erythroid colony-forming abilities of bone marrow cells from 17 patients with MDS. The effects of normal donor-derived marrow were examined in comparison. Suppression of erythroid colony formation in MDS in response to Epo could not be restored by the addition of interleukin-3 (IL-3) to culture. In cultures dishes supplemented with KL, erythroid colony formation was dramatically enhanced, regarding both colony number and size. Colony-forming abilities by MDS progenitors were improved following costimulation with KL, particularly in refractory anemia (RA) and refractory anemia with ring sideroblasts (RARS); however, little enhancement was apparent following KL stimulation of marrow from patients with refractory anemia with excess of blasts (RAEB), refractory anemia with excess of blasts in transformation (RAEB-t), and chronic myelomonocytic leukemia (CMML). These results suggest that KL responsiveness of patients with low-risk MDS may still be intact, and that with progression to high-risk MDS, erythroid progenitors lose proliferative reactivity to both KL and Epo stimulation. KL may have a therapeutic role in restoring erythropoiesis in a subset of patients with MDS.
