PMID- 12100164 OWN - NLM STAT- MEDLINE DCOM- 20020911 LR - 20190705 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 118 IP - 1 DP - 2002 Jul TI - All-trans retinoic acid prevents apoptosis of human marrow CD34+ cells deprived of haematopoietic growth factors. PG - 289-95 AB - The regulation of apoptosis plays a key role in haematopoiesis. It has been demonstrated that haematopoietic progenitor cells progressively undergo apoptotic cell death in the absence of appropriate growth factors. We studied the effects of pharmacological doses of all-transretinoic acid (ATRA) on the apoptosis of human adult marrow CD34+ progenitor cells cultured for 7 d in a serum-free medium. We quantified CD34+ cells, clonogenic progenitors and 5 week colony-forming cells (CFC) before and after ATRA exposure. Moreover, we defined the apoptotic status of the CD34+ cell fraction by analysis of phosphatidylserine externalization (using annexin V), the relative membrane permeability to 7-aminoactinomycin D (7AAD) and the mitochondrial membrane potential [using 3,3'-dihexyloxacarbocyanine iodide, DiOC6(3)]. In the drastic experimental conditions used, a decrease in viable CD34+ cells, granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E) and 5 week CFC were observed. Exposure to ATRA partially prevented the decrease in viable CD34+, without a concomitant effect on the clonogenic and more immature progenitors. ATRA-treated CD34+ cells displayed changes in apoptotic status compared with control cultures, particularly in lower annexin V-binding. These results were confirmed using 7AAD and DiOC6(3). Our results demonstrate that ATRA exerts a protective effect on CD34+ cells exposed to such apoptotic stress. FAU - Herault, Olivier AU - Herault O AD - EA-3249 'Cellules Hematopoietiques, Hemostase et Greffe' Faculty of Medicine, University Hospital, Tours, France. olivier.herault@med.univ-tours.fr FAU - Domenech, Jorge AU - Domenech J FAU - Georget, Marie Therese AU - Georget MT FAU - Clement, Nathalie AU - Clement N FAU - Colombat, Philippe AU - Colombat P FAU - Binet, Christian AU - Binet C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Annexins) RN - 0 (Antigens, CD34) RN - 0 (Antineoplastic Agents) RN - 0 (Culture Media, Serum-Free) RN - 5688UTC01R (Tretinoin) SB - IM MH - Annexins/metabolism MH - *Antigens, CD34 MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/*drug effects MH - Bone Marrow Cells/*drug effects/immunology/metabolism MH - Cell Survival MH - Cells, Cultured MH - Clone Cells MH - Culture Media, Serum-Free MH - Humans MH - Protein Binding MH - Time Factors MH - Tretinoin/*pharmacology EDAT- 2002/07/09 10:00 MHDA- 2002/09/12 10:01 CRDT- 2002/07/09 10:00 PHST- 2002/07/09 10:00 [pubmed] PHST- 2002/09/12 10:01 [medline] PHST- 2002/07/09 10:00 [entrez] AID - 3573 [pii] AID - 10.1046/j.1365-2141.2002.03573.x [doi] PST - ppublish SO - Br J Haematol. 2002 Jul;118(1):289-95. doi: 10.1046/j.1365-2141.2002.03573.x.