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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2461-2470
Stem Cell Factor as a Single Agent Induces Selective
Proliferation of the Philadelphia Chromosome Positive Fraction
of Chronic Myeloid Leukemia CD34+ Cells
Sarah Moore,
David N. Haylock,
Jean-Pierre Lévesque,
Louise
A. McDiarmid,
Leanne M. Samels,
L. Bik To,
Paul J. Simmons, and
Timothy
P. Hughes
From the Leukemia Research Laboratory, Division of Haematology,
Hanson Centre for Cancer Research, IMVS, Adelaide, SA, Australia.
The interaction between p145c-KIT and
p210bcr-abl in transduced cell lines, and the selective
outgrowth of normal progenitors during long-term culture of chronic
myeloid leukemia (CML) cells on stroma deficient in stem-cell factor
(SCF) suggests that the response of CML cells to SCF may be abnormal.
We examined the proliferative effect of SCF(100 ng/mL), provided as the
sole stimulus, on individual CD34+ cells from five normal
donors and five chronic-phase CML patients. Forty-eight percent of
isolated single CML CD34+ cells proliferated after 6 days
of culture to a mean of 18 cells, whereas only 8% of normal
CD34+ cells proliferated (mean number of cells generated
was 4). SCF, as a single agent, supported the survival and expansion of
colony-forming unit-granulocyte-macrophage (CFU-GM) from CML
CD34+CD38+ cells and the more primitive CML
CD34+CD38 cells. These CFU-GM colonies
were all bcr-abl positive, showing the specificity of SCF stimulation
for the leukemic cell population. Coculture of CML and normal
CD34+ cells showed exclusive growth of Ph+
cells, suggesting that growth in SCF alone is not dependent on secretion of cytokines by CML cells. SCF augmentation of
 1-integrin-mediated adhesion of CML CD34+
cells to fibronectin was not increased when compared with the effect on
normal CD34+ cells, suggesting that the proliferative and
adhesive responses resulting from SCF stimulation are uncoupled. The
increased proliferation may contribute to the accumulation of leukemic
progenitors, which is a feature of CML.
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