Modulation of in vitro chemosensitivity in acute myelogenous leukemia cell line by GM-CSF: opposing effects observed with different cytotoxic drugs and time exposure

Abstract

In some studies the GM-CSF (granulocyte-macrophage colony-stimulating factor) increased the in vitro sensitivity of acute myeloid leukemia (AML) cells to cytosine arabinoside (Ara-C), however, in clinical trials no favorable effects were shown. We used a GM-CSF responsive AML cell line (AML 193) to test the effects of growth stimulation on in vitro efficacy of Ara-C and methotrexate (MTX). In 6 days continuous exposure, dose dependent Ara-C cytotoxicity was counteracted by GM-CSF. Conversely, MTX cytotoxicity was increased significantly. However, in a short term treatment (24 h, high doses) the GM-CSF increased both MTX and Ara-C cytotoxicity. These effects might depend on different drug regimens and cell features.