Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2569-2577
Optimal Proliferation of a Hematopoietic Progenitor Cell Line
Requires Either Costimulation With Stem Cell Factor or Increase of
Receptor Expression That Can Be Replaced by Overexpression of Bcl-2
Huei-Mei Huang,
Jian-Chiuan Li,
Yueh-Chun Hsieh,
Hsin-Fang Yang-Yen, and
Jeffrey Jong-Young Yen
From the Institute of Biomedical Sciences and Institute of Molecular
Biology, Academia Sinica, Taipei, Taiwan; and Graduate Institute of
Life Sciences, National Defense Medical Center, Taipei, Taiwan.
In vitro proliferation of hematopoietic stem cells requires
costimulation by multiple regulatory factors whereas expansion of
lineage-committed progenitor cells generated by stem cells usually
requires only a single factor. The distinct requirement of factors for
proliferation coincides with the differential temporal expression of
the subunits of cytokine receptors during early stem cell
differentiation. In this study, we explored the underlying mechanism of
the requirement of costimulation in a hematopoietic progenitor cell
line TF-1. We found that granulocyte-macrophage colony-stimulating
factor (GM-CSF) optimally activated proliferation of TF-1 cells
regardless of the presence or absence of stem cell factor (SCF).
However, interleukin-5 (IL-5) alone sustained survival of TF-1 cells
and required costimulation of SCF for optimal proliferation. The
synergistic effect of SCF was partly due to its anti-apoptosis activity. Overexpression of the IL-5 receptor 
subunit (IL5R) in
TF-1 cells by genetic selection or retroviral infection also resumed
optimal proliferation due to correction of the defect in apoptosis
suppression. Exogenous expression of an oncogenic anti-apoptosis
protein, Bcl-2, conferred on TF-1 cells an IL-5-dependent phenotype.
In summary, our data suggested SCF costimulation is only necessary when
the expression level of IL5R is low and apoptosis suppression is
defective in the signal transduction of IL-5. Expression of Bcl-2
proteins released the growth restriction of the progenitor cells and
may be implicated in leukemia formation.
