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Growth factors influence the sensitivity of leukemic stem cells to cytosine
arabinoside in culture
J Miyauchi, CA Kelleher, C Wang, S Minkin and EA McCulloch
Ontario Cancer Institute, Toronto, Canada.
We have proposed that the blasts in acute myeloblastic leukemia (AML) are
renewal populations maintained by a small subpopulation of stem cells. The
balance between self-renewal and differentiation in blast stem cells may be
an important attribute contributing to treatment outcome. Cytosine
arabinoside (ara-C) is included in most chemotherapeutic regimens for the
treatment of AML. When ara-C survival curves are constructed, the drug
appears to be more toxic when an assay is used that detects principally
self-renewing divisions, compared with a procedure that depends on terminal
divisions. AML blasts usually respond in culture to myelopoietic growth
factors; their response often includes a change in self-renewal,
differentiation, or both. These features of the model for AML blasts led to
the prediction that growth factors would alter ara-C survival curves in a
way that depended on the effects of the culture conditions on self-renewal
and differentiation. Four AML blast populations were chosen to test this
prediction on the basis of our ability to manipulate them by adding or
withholding one or more growth factors. Highly significant changes were
seen in the ara-C survival curves, depending on the growth factors present
in the cultures as was predicted by the observed effects of the factors on
renewal and differentiation.
Volume 73,
Issue 5,
pp. 1272-1278,
04/01/1989
Copyright © 1989 by The American Society of Hematology
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