Heterogeneous Effects of G-CSF and GM-CSF on Cell Growth and Ara-C Cytotoxicity in Childhood Leukemias Which Express Myeloid Markers

Abstract

It is uncertain if acute lymphoblastic leukemia (ALL) cells expressing myeloid makers can respond to granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). We investigated the effects of G-CSF (0.01 μg/ml) and GM-CSF (0.01 μg/ml) on [³H]thymidine (TdR) uptake, and the cytotoxicity of l-β-D-arabinofuranosylcytosine (ara-C) in leukemia cells from 17 pediatric patients. ALL cells without myeloid markers did not respond to G-CSF or GM-CSF. On the other hand, these cytokines enhanced the [³H]TdR uptake and cell growth, not only of AML cells but also of ALL cells expressing myeloid antigens. However, G-CSF and GM-CSF did not always enhance the growth inhibitory effect of the cell cycle specific drug ara-C when the cells were co-cultured with the drug. There was no relationship between cell growth and the amount of [³H]TdR incorporation or the intracellular ara-CTP level. These results indicate the heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C sensitivity in childhood leukemia cells.

Key Words:

• G-CSF
• GM-CSF
• ara-C
• MTT assay
• [³H]thymidine
• incorporation assay
• mixed lineage leukemia
• biphenotypic leukemia