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 microgram/ml) and GM-CSF (0.01 microgram/ml) on [3H]thymidine (TdR) uptake, and the cytotoxicity of 1-beta-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.

Granulocyte Colony Stimulating Factor Increases Drug Resistance of Leukaemic Blast Cells to Daunorubicin

“…There are several reports, however, implying that some B-or T-cell leukaemias, biphenotypic leukemia cells, or leukaemic cells with specific translocations may express G-CSF receptors and are able to respond to exogenous G-CSF [23,24,[26][27][28]. In the present work we studied how G-CSF in cell suspension influences the drug sensitivity of KG-1 leukaemic cells.…”

“…Oh et al observed that G-CSF receptor expression was increased in relapsed or refractory ALL and a significant correlation between G-CSFR and GM-CSFR expression was found [32]. Based on the above studies the question arises whether G-CSF used as a component of supportive treatment of childhood ALL with febrile neutropenia can lead to proliferation of not only the normal myeloid cells but of lymphoid leukaemic blasts, that coexpress myeloid markers as well [28]. In addition, whether or not G-CSF influences drug sensitivity of blast cells remains to be answered, too.…”

“…Another study demonstrated that G-CSF can stimulate proliferation of adult T-cell lymphoma cells [31]. It was also shown that the growth inhibitory effect of cytarabine was heterogeneous depending upon the presence of G-CSF in cultured lymphoblastic leukaemia cells [28]. E.-J.…”

“…There are several reports suggesting that some ALL cells with B-or T-cell surface antigens [23,24], or biphenotypic leukemia cells [25] express G-CSF receptors and they are able to respond to exogenously added G-CSF [23,24,[26][27][28]. de Lau et al pointed out that the gene encoding for the G-CSF receptor is specifically upregulated in pre-B cells with (1;19)(q23;p13.3) translocation, which can be detected in 25-30% of childhood pre-B ALL [29,30] as a nonrandom chromosome abnormality.…”

Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia

“…There are a few reports that some ALL cells express G-CSF and GM-CSF receptors and/or respond to these myelopoietic cytokines (Drach et al 1994;Freedman et al 1993;Higashigawa et al 1996;Komada et al 1993;Ohno 1994;Shimoda et al 1992;Shinjo et al 1997). Other studies, however, failed to confirm the presence of receptors to myelopoietic cytokines on ALL cells (Park et al 1989;Piao and Okabe 1990;Tomeczkowski et al 1995).…”