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Both Stroma and Stem Cell Factor Maintain Long-Term Growth of ELM
Erythroleukemia Cells, but Only Stroma Prevents Erythroid
Differentiation in Response to Erythropoietin and Interleukin-3
Jim O'Prey,
Nick Leslie,
Katsukiko Itoh,
Wolfram Ostertag,
Chris Bartholomew, and
Paul R. Harrison
From the Beatson Institute for Cancer Research, CRC Beatson
Laboratories, Bearsden, Glasgow; the Department of Clinical Medical
Biology, Kyoto University, Kyoto, Japan; and Heinrich Pette Institut
for Experimental Virology and Immunology, Hamburg University, Hamburg,
Germany.
Defining how the stromal requirements of hematopoietic progenitors
change during leukemia progression is an important topic that is not
well understood at present. The murine ELM erythroleukemia is an
interesting model because the erythroid progenitors retain dependence
on bone marrow-derived stromal cells for long-term growth in vitro, and
they also undergo erythroid differentiation in the presence of
erythropoietin (EPO) and interleukin-3 (IL-3). In this report, we have
shown using neutralizing antibodies that stem cell factor (SCF),
insulin-like growth factor (IGF)-1, and integrin signaling
pathways are all involved. We then determined whether ELM cells can be
maintained long-term without stroma in various combinations of growth
factors produced by stroma cells or growth factors for which ELM cells
have receptors. This showed that ELM cells could be maintained with
high efficiency in SCF alone; furthermore, the cells remained
absolutely SCF-dependent and did not become more tumorigenic than cells
maintained on stroma. In contrast, ELM cells underwent clonal
extinction when serially cloned in IGF1; any cells that survived
long-term growth in IGF-1 were found to be IGF1-independent. One
important difference between maintaining ELM cells on stroma and growth
in SCF is that stroma reversibly inhibits their differentiation in
response to EPO and IL-3, whereas SCF does not.
Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1548-1555
© 1998 by The American Society of Hematology.
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