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Flt3high and Flt3low CD34+
Progenitor Cells Isolated From Human Bone Marrow Are Functionally
Distinct
Katharina S. Götze,
Manuel Ramírez,
Kelly Tabor,
Donald Small,
William Matthews, and
Curt I. Civin
From the Division of Pediatric Oncology, Departments of Oncology and
Pediatrics, Johns Hopkins University School of Medicine, Baltimore MD;
and Genentech Inc, South San Francisco, CA.
We generated monoclonal antibodies against the human Flt3 receptor
and used them to study the characteristics of normal human bone marrow
cells resolved based on Flt3 expression. Human CD34+ or
CD34+lin marrow cells were sorted into two
populations: cells expressing high levels of Flt3 receptor
(Flt3high) and cells with little or no expression of Flt3
receptor (Flt3low). Flt3 receptor was detected on a subset
of CD34+CD38 marrow cells, as well as on
CD34+CD19+ B lymphoid progenitors and
CD34+CD14+CD64+ monocytic
precursors. Flt3 receptor was also present on more mature
CD34CD14+ monocytes. In colony-forming
assays, Flt3high cells gave rise mainly to colony-forming
unit-granulocyte-macrophage (CFU-GM) colonies, whereas
Flt3low cells produced mostly burst-forming unit-erythroid
colonies. There was no difference in the number of multilineage CFU-Mix colonies between the two cell fractions. Cell cycle analysis showed that a large number of the Flt3low cells were in the
G0 phase of the cell cycle, whereas Flt3high
cells were predominantly in G1. Cell numbers in the
suspension cultures initiated with Flt3high cells were
maintained in the presence of Flt3 ligand (FL) alone, and increased in
response to FL plus kit ligand (KL). In contrast, cell numbers in the
suspension cultures started with Flt3low cells did not
increase in the presence of FL, or FL plus KL. Upregulation of Flt3
receptor on Flt3low cells was not detected during
suspension culture. CD14+ monocytes were the major cell
type generated from
CD34+linFlt3high cells in
liquid suspension culture, whereas cells generated from CD34+linFlt3low cells were
mainly CD71+GlycA+ erythroid cells. These
results show clear functional differences between
CD34+Flt3high and
CD34+Flt3low cells and may have implications
concerning the in vitro expansion of human hematopoietic progenitor
cells.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 1947-1958
© 1998 by The American Society of Hematology.
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