title: All-trans retinoic acid at low concentration directly stimulates normal adult megakaryocytopoiesis in the presence of thrombopoietin or combined cytokines.
abstract: In order to investigate the direct effects of retinoids on normal adult hematopoietic progenitors, purified CD34+ cells were seeded in serum-free cultures in the presence of pharmacological (10(-6)) M or physiological (10(-12)) M concentrations of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) plus combinations of specific cytokines. 10(-6) M ATRA and 9-cis RA significantly decreased the number of granulomacrophagic, erythroid and megakaryocytic (CFU-meg) progenitors. On the other hand, 10(-12) M ATRA significantly promoted the growth of CFU-meg, in the presence either of thrombopoietin or of IL-3+ GM-CSF, and induced a reproducible stimulation of the immature CD34+DR- subset. In conclusion, our findings suggest that retinoic acids probably play a direct role in normal adult hematopoietic development at both physiological and pharmacological concentrations. The stimulatory effect on megakaryocytopoiesis should be considered in the perspective of a potential use of low-dose ATRA, combined with thrombopoietin or other cytokines, in pathological conditions where the megakaryocytic compartment is impaired and the stimulation of megakaryocytopoiesis is requested.
authors.affiliation: Insititute of Hematology and Medical Oncology Serágnoli, University of Bologna, Italy. Gvisani@med.unibo.it
authors.forename: G
authors.initials: G
authors.lastname: Visani
authors.forename: E
authors.initials: E
authors.lastname: Ottaviani
authors.forename: G
authors.initials: G
authors.lastname: Zauli
authors.forename: P
authors.initials: P
authors.lastname: Tosi
authors.forename: A
authors.initials: A
authors.lastname: Pellacani
authors.forename: A
authors.initials: A
authors.lastname: Isidori
authors.forename: S
authors.initials: S
authors.lastname: Pierpaoli
authors.forename: S
authors.initials: S
authors.lastname: Tura
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D013926:Thrombopoietin / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D007377:Interleukin-3; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin