title: Diamond-blackfan anemia: in vitro response of erythroid progenitors to the ligand for c-kit.
abstract: To provide insights into the pathogenesis of Diamond-Blackfan anemia, we examined the in vitro response of erythroid progenitors to the recently isolated ligand for c-kit (stem cell factor, SCF). For these studies, marrow or blood mononuclear cells from 10 Diamond-Blackfan patients were cultured with erythropoietin (Ep), Ep and interleukin-3, Ep and granulocyte-macrophage colony-stimulating factor, or Ep and lymphocyte conditioned media (LCM). These combinations were tested in the presence or absence of SCF. The mean number of cells per erythroid burst increased 5 to 50-fold in cultures containing SCF. Furthermore, many additional erythroid bursts were seen (mean increment 3.2 x baseline values). Although burst-forming unit-erythroid (BFU-E) from all patients responded, there were differences among individuals in the sensitivity of their BFU-E to SCF. In six patients and all control studies, plateau frequencies of erythroid bursts were achieved with less than or equal to 10 ng/mL SCF, whereas in studies from the other four patients, over 50 ng/mL SCF was required. These data invite speculation that the c-kit receptor/ligand axis is involved in the pathogenesis of Diamond-Blackfan anemia. More importantly and regardless of whether the observed patterns of response reflect the primary defect or an epiphenomenon, our data strongly support a therapeutic trial of SCF in patients with Diamond-Blackfan anemia.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: J L
authors.initials: JL
authors.lastname: Abkowitz
authors.forename: K M
authors.initials: KM
authors.lastname: Sabo
authors.forename: B
authors.initials: B
authors.lastname: Nakamoto
authors.forename: C A
authors.initials: CA
authors.lastname: Blau
authors.forename: F H
authors.initials: FH
authors.lastname: Martin
authors.forename: K M
authors.initials: KM
authors.lastname: Zsebo
authors.forename: T
authors.initials: T
authors.lastname: Papayannopoulou
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003470:Culture Media; D015672:Erythroid Precursor Cells / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology; D005199:Fanconi Anemia / Q000473:pathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D019089:Stem Cell Factor
chemical_list: D003470:Culture Media; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor