Effect of a new retinoidal benzoic acid derivative on normal human hematopoietic progenitor cell growth in vitro.
13-cis-Retinoic acid (RA) has been demonstrated to alter hemopoiesis in vitro. We compared proliferation and differentiation effects of RA to a synthetic retinoid, (E)-4-[2-(5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl-1-propenyl]benzoic acid (TTNPB), on human normal bone marrow cells. TTNPB stimulated the in vitro growth of erythroid-granulocyte-macrophage progenitors and erythroid progenitors. Dose-response curves showed that maximal increments of erythroid-granulocyte-macrophage progenitor growth [173 +/- 17% (SE)] and erythroid progenitor growth [210 +/- 40%] occurred with TTNPB at 10(-9) M. With RA, there was maximal increment (173 +/- 21%) for erythroid progenitors only, and that at 10(-8) M. Evaluating clonogenicity of marrow cells in the presence of the two retinoic acid derivatives demonstrated that TTNPB and RA enhanced myeloid colony (CFU-C) growth; maximal stimulation occurred at 10(-6) M (130 +/- 8% and 161 +/- 5% increment for TTNPB and RA, respectively). The two retinoic acid analogues did not alter the differentiation pattern of myeloid colonies (macrophage colonies, granulocytic colonies, or granulocyte-macrophage colonies). Replating studies showed that the formation of secondary hemopoietic colonies was not altered following incubation of hemopoietic progenitors with TTNPB or RA. These data demonstrate that TTNPB is more active than RA in stimulating the growth of hemopoietic progenitors from normal marrows. Such findings may have therapeutic implications for various hemopoietic disorders.
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Fabian
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Shvartzmayer
D001565:Benzoates / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D001565:Benzoates; D012176:Retinoids; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid