title: Erythropoiesis in myelodysplastic syndrome: expression of receptors for erythropoietin and kit ligand.
abstract: Ineffective erythropoiesis due to an impaired response to erythropoietin (EPO) is a prominent abnormality in myelodysplastic syndromes (MDS). The growth factor kit ligand (KL) may restore the in vitro erythroid colony-forming response to EPO in a subset of patients. The inability of MDS erythroid progenitors to react properly to EPO and/or KL has not been resolved. We have investigated erythropoietin receptor (EPO-R) and KL receptor (c-kit) expression in 15 cases of MDS by FACS analysis. The percentage of bone marrow cells expressing the EPO-R from patients with MDS were comparable to normal marrow. No apparent correlation was found between the number of MDS cells coexpressing the EPO-R and CD34 and impaired erythroid response. C-kit was expressed in most MDS patients, including those not responding to KL in EPO-induced cultures. In nine MDS cases the different splice variants of the EPO-R were analyzed. MDS cells, like normal marrow, expressed the full length EPO-R. These results show that impaired erythroid response in MDS cannot be explained by a quantitative lack of receptors for EPO or KL and that most likely suppression of erythroid response is caused by defective receptor signalling following ligand binding, representing a functional defect within the receptor itself or at a level downstream of the receptor.
authors.affiliation: Dr Daniel den Hoed Cancer Center, Department of Hematology, Rotterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Backx
authors.forename: L
authors.initials: L
authors.lastname: Broeders
authors.forename: L H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: B
authors.initials: B
authors.lastname: Wognum
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012326:RNA Splicing; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D017467:Receptors, Erythropoietin; D019009:Proto-Oncogene Proteins c-kit