title: Unimpaired terminal erythroid differentiation and preserved enucleation capacity in myelodysplastic 5q(del) clones: a single cell study.
abstract: BACKGROUND
  Anemia is a characteristic of myelodysplastic syndromes, such as the rare 5q- syndrome, but its mechanism remains unclear. In particular, data are lacking on the terminal phase of differentiation of erythroid cells (enucleation) in myelodysplastic syndromes.
  
  
  METHODS
  We used a previously published culture model to generate mature red blood cells in vitro from human hematopoietic progenitor cells in order to study the pathophysiology of the 5q- syndrome. Our model enables analysis of cell proliferation and differentiation at a single cell level and determination of the enucleation capacity of erythroid precursors.
  
  
  RESULTS
  The erythroid commitment of 5q(del) clones was not altered and their terminal differentiation capacity was preserved since they achieved final erythroid maturation (enucleation stage). The drop in red blood cell production was secondary to the decrease in the erythroid progenitor cell pool and to impaired proliferative capacity. RPS14 gene haploinsufficiency was related to defective erythroid proliferation but not to differentiation capacity.
  
  
  CONCLUSIONS
  The 5q- syndrome should be considered a quantitative rather than qualitative bone marrow defect. This observation might open the way to new therapeutic concepts.
authors.affiliation: INSERM, UMR_S 938, Paris, France. laurent.garderet@sat.aphp.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Ladan
authors.initials: L
authors.lastname: Kobari
authors.forename: Christelle
authors.initials: C
authors.lastname: Mazurier
authors.forename: Caroline
authors.initials: C
authors.lastname: De Witte
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Giarratana
authors.forename: Christine
authors.initials: C
authors.lastname: Pérot
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Hélène
authors.initials: H
authors.lastname: Lapillonne
authors.forename: Luc
authors.initials: L
authors.lastname: Douay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004912:Erythrocytes / Q000166:cytology*; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D012269:Ribosomal Proteins / Q000235:genetics
chemical_list: D012269:Ribosomal Proteins; C039747:ribosomal protein S14