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Heterogeneous Effects of G-CSF and GM-CSF on Cell Growth and Ara-C Cytotoxicity in Childhood Leukemias Which Express Myeloid Markers
Authors:Masamune Higashigawa  Hiroshi Kuwabara  De-Chen Cao  Hiroki Hori  Toshiki Ohkubo  Hajime Kawasaki  Masaru Ido  Yoshihiro Komada  Minoru Sakurai
Institution:  a Department of Pediatrics, Mie University School of Medicine, Tsu, Mie, Japan
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.
Keywords:G-CSF  GM-CSF  ara-C  MTT assay  [3H]thymidine  incorporation assay  mixed lineage leukemia  biphenotypic leukemia
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