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All‐ trans retinoic acid at low concentration directly stimulates normal adult megakaryocytopoiesis in the presence of thrombopoietin or combined cytokines
Author(s) -
Visani Giuseppe,
Ottaviani Emanuela,
Zauli Giorgio,
Tosi Patrizia,
Pellacani Annalisa,
Isidori Alessandro,
Pierpaoli Sabina,
Tura Sante
Publication year - 1999
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1999.tb01762.x
Subject(s) - megakaryocytopoiesis , thrombopoietin , retinoic acid , haematopoiesis , progenitor cell , megakaryocyte , endocrinology , medicine , stimulation , biology , stem cell , microbiology and biotechnology , biochemistry , gene
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.