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Long-term culture of chronic myelogenous leukemia marrow cells on stem cell
factor-deficient stroma favors benign progenitors
R Agarwal, S Doren, B Hicks and CE Dunbar
Children's Hospital Medical Center, Cincinnati, OH.
Long-term culture of marrow from patients with chronic myelogenous leukemia
(CML) has been reported to favor the outgrowth of bcr/abl- progenitor cells
in some patients. We examined the effect of the presence of soluble or
transmembrane forms of stem cell factor (SCF) in long-term cultures of CML
marrow. CD34-enriched cells from CML patients in advanced chronic phase or
accelerated phase were plated on immortalized fetal liver stromal cells
from homozygous SCF-deficient SI/SI mice (SI/SI4) with or without the
addition of soluble human SCF, SI/SI4 cells expressing high levels of the
transmembrane form of human SCF (SI/SIh220), or primary human allogeneic
stroma. Cells were removed from cultures and plated weekly in colony
assays. The clonagenic cell output from cultures completely lacking SCF was
lower over the first 2 to 3 weeks, but by 5 weeks was similar to the
clonagenic cell output from the other culture conditions. Analysis of
bcr/abl transcripts from individual colonies showed a lower percentage of
malignant progenitors present in long-term cultures completely deficient in
SCF than under the other culture conditions, particularly compared with
primary human stroma-containing long-term cultures. SCF may specifically
favor malignant versus benign progenitor cells present in the marrow of CML
patients, and an abnormal proliferative response to SCF in very primitive
cells may be an underlying defect in the pathophysiology of this disease.
Volume 85,
Issue 5,
pp. 1306-1312,
03/01/1995
Copyright © 1995 by The American Society of Hematology
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