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Treatment with interleukin-3 plus granulocyte-macrophage colony-
stimulating factors improves the selectivity of Ara-C in vitro against
acute myeloid leukemia blasts
K Bhalla, C Holladay, Z Arlin, S Grant, AM Ibrado and M Jasiok
Department of Medicine, Medical University of South Carolina, Charleston
29425.
Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and
granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have
been shown to increase the percentage of acute myeloid leukemia (AML)
blasts in S phase and enhance the cytotoxic effects of Ara-C against these
blasts in culture. We compared in vitro the effects of a combined treatment
with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and
cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and
AML blasts. NBMMC from six healthy volunteers and AML blasts from 10
patients were incubated for 20 hours with or without IL- 3 plus GM-CSF,
followed by a concurrent treatment with Ara-C for 4 additional hours.
Exposure to the HGFs and Ara-C produced significantly higher intracellular
Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as
compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA
incorporation that was significantly higher in AML blasts versus NBMMC.
This selective improvement of Ara-C metabolism in AML blasts was associated
with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth
inhibition. In contrast, exposure to HGFs resulted in an improved colony
growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid,
monocyte, megakaryocyte. These in vitro studies indicate that a combined
treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C
against AML blasts.
Volume 78,
Issue 10,
pp. 2674-2679,
11/15/1991
Copyright © 1991 by The American Society of Hematology
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