title: Kit ligand improves in vitro erythropoiesis in myelodysplastic syndrome.
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.
authors.affiliation: Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Backx
authors.forename: L
authors.initials: L
authors.lastname: Broeders
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000097:blood; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000503:physiopathology*; D019089:Stem Cell Factor
chemical_list: D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor