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Bhalla, K. et al.

Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts.

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.[1]

References

Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts. Bhalla, K., Holladay, C., Arlin, Z., Grant, S., Ibrado, A.M., Jasiok, M. Blood (1991) [Pubmed]

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