Quiescent (5-fluorouracil-resistant) aplastic anemia hematopoietic cells in vitro

Experimental Hematology
Sian RizzoF M Gibson

Abstract

Bone marrow from aplastic anemia (AA) patients shows reduced numbers in long-term culture (LTC)-initiating cell (LTC-IC) assays. The LTC-IC assay is based on assumptions of the culture kinetics of normal hematopoietic stem cells (HSC), which are not necessarily justified in a disease state. We therefore undertook a detailed examination of the kinetics of quiescent HSC from AA patients in LTC. Colony formation by quiescent HSC in LTC was tested by pretreating control (n=6) and AA bone marrow (n=7) with 5-fluorouracil. Secondly, we manipulated normal samples to inoculate cultures with proportions of CD34+ cells similar to those from AA samples. We obtained enough CD34+ cells to reconstitute one AA sample to "normal" levels. Patient cells showed altered kinetics with rapid proliferation and premature termination of LTC. In vivo, decreased numbers of HSC may induce rapid proliferation and differentiation; a similar phenomenon could explain the observations in culture. We therefore manipulated normal samples to contain a proportion of CD34+ HSC similar to that in AA samples. Although absolute numbers of secondary colonies in LTC were reduced, the kinetics of culture were not altered. However, when AA CD34+ HSC were reconstituted to ...Continue Reading

References

Jun 1, 1991·British Journal of Haematology·J C MarshT M Dexter
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H J SutherlandC J Eaves
Jul 1, 1990·British Journal of Haematology·F M Gibson, E C Gordon-Smith
Mar 1, 1989·International Journal of Cell Cloning·H S JunejaF H Gardner
Mar 1, 1984·The Journal of Experimental Medicine·G Van Zant
Feb 1, 1994·British Journal of Haematology·J ScopesF M Gibson
Jun 1, 1994·British Journal of Haematology·J P MaciejewskiN S Young
Mar 8, 2000·Acta Haematologica·B M Camitta
Oct 23, 2002·The Hematology Journal : the Official Journal of the European Haematology Association·Sian RizzoFrances M Gibson

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