title: In vitro growth and regulation of bone marrow enriched CD34+ hematopoietic progenitors in Diamond-Blackfan anemia.
abstract: Diamond-Blackfan anemia (DBA) is a congenital red blood cell aplasia. No clear explanation has been given of its defective erythropoiesis, although different humoral or cellular inhibitory factors have been proposed. To clarify the nature of this defect we studied the effect of several human recombinant growth factors on an enriched CD34+ population obtained from the bone marrow of 10 DBA patients. We observed a defect underlying the early erythroid progenitors, which were unresponsive to several growth factors (erythropoietin, interleukin-3 [IL-3], IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], erythroid potentiating activity), either alone or in association. The production of cytokines was not impaired, and high levels of IL-3 and GM-CSF were found in phytohemagglutinin-leukocyte-conditioned medium (PHA-LCM) when tested with a sensitive biologic assay on the M-07E cell line. Hematopoietic stem cells in DBA patients may be induced to differentiate to the granulocyte megakaryocyte, but not the erythroid compartment, as shown after CD34+ cell preincubation with IL-3. Addition of the stem cell factor to IL-3 and erythropoietin induces a dramatic in vitro increase in both the number and the size of BFU-E, which also display a normal morphologic terminal differentiation.
authors.affiliation: Institute of Histology and General Embryology, Giorgio Prodi, Interdepartmental Center for Cancer Research, Italy.
authors.forename: G P
authors.initials: GP
authors.lastname: Bagnara
authors.forename: G
authors.initials: G
authors.lastname: Zauli
authors.forename: L
authors.initials: L
authors.lastname: Vitale
authors.forename: P
authors.initials: P
authors.lastname: Rosito
authors.forename: V
authors.initials: V
authors.lastname: Vecchi
authors.forename: G
authors.initials: G
authors.lastname: Paolucci
authors.forename: G C
authors.initials: GC
authors.lastname: Avanzi
authors.forename: U
authors.initials: U
authors.lastname: Ramenghi
authors.forename: F
authors.initials: F
authors.lastname: Timeus
authors.forename: V
authors.initials: V
authors.lastname: Gabutti
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001853:Bone Marrow / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; 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 / Q000096:biosynthesis / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008297:Male
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D003470:Culture Media; D006133:Growth Substances; D007377:Interleukin-3; D015850:Interleukin-6; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor