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Poster (Scientific congresses and symposiums)
Thrombopoietin dose-response curves reflect the number of doublings undergone by human megakaryocyte progenitors
Paulus, Jean-Michel; Debili, N.; Larbret, F. et al.
200433rd Annual Meeting of the International Society for Experimental Hematology (ISEH)
 

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Abstract :
[en] To assess the variation of thrombopoietin (TPO) responsiveness associated with MK progenitor amplification, TPO dose-response curves were obtained for MK clones derived from normal human CD34+CD41+ cells which had been single-cell plated in serum-deprived medium with TPO concentrations of 0-1000 pg/mL per well. On day 5, the number of MK cells per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the means of the frequency of clones of each size vs logTPO concentration showed highly significant differences in the TPO concentration needed for half-maximum generation of clones of different sizes (TPO50). Based on 3 independent experiments, TPO50, expressed in pg/mL, was 1.89 ±SD 0.87 for 1 cell MK clone; 7.75 ±1.40 for 2-3 cell MK clone; 38.5 ±8.73 for 4-7 cell MK clone and 93.6 ±27.7 for 8-15 cell MK clone (p<0.001). Compared to the CD42- fraction of CD34+CD41+ progenitors, the corresponding CD42+ fraction had a lower TPO50 (p<0.001), underwent lesser NbD (p<0.001) and expressed a 10-fold greater mean mpl receptor density. In order to interpret the conclusion that the most responsive progenitors were those which proliferated less, we tested a prediction of the generation-age model, namely that the percentage of progenitors undergoing a given number of residual doublings in vitro (NbDr) depends on the number of previous doublings they had undergone in vivo (NbDp). It was demonstrated that logTPO50 had a positive correlation with NbDr and negative correlation with NbDp (p<0.001). The reciprocal relationship between NbDp and NbDr was evidence for a generation-age model in which TPO responsiveness increases by a factor of approximately 4 per doubling. This model suggests that progenitors which have completed their proliferative program have maximum factor responsiveness and are preferentially induced to terminal differentiation.
Disciplines :
Hematology
Laboratory medicine & medical technology
Author, co-author :
Paulus, Jean-Michel ;  Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Debili, N.
Larbret, F.
Levin, J.
Vainchenker, W.
Language :
English
Title :
Thrombopoietin dose-response curves reflect the number of doublings undergone by human megakaryocyte progenitors
Publication date :
July 2004
Event name :
33rd Annual Meeting of the International Society for Experimental Hematology (ISEH)
Event organizer :
ISEH
Event place :
New Orleans, United States - Louisiana
Event date :
Saturday, July 17–Tuesday, July 20, 2004
Audience :
International
Available on ORBi :
since 09 June 2016

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