Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers.
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.
Higashigawa
M
M
Department of Pediatrics, Mie University School of Medicine, Japan.
Kuwabara
H
H
Cao
D C
DC
Hori
H
H
Ohkubo
T
T
Kawasaki
H
H
Ido
M
M
Komada
Y
Y
Sakurai
M
M
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D003561:Cytarabine; D014316:Tritium; D001085:Arabinofuranosylcytosine Triphosphate; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013936:Thymidine