Recombinant lymphotoxin enhances the growth of normal, but not of chronic myeloid leukemic, human hematopoietic progenitor cells in vitro.
The effects of recombinant lymphotoxin (rLT) and tumor necrosis factor (rTNF) on the growth of clonogenic normal and leukemic hematopoietic cells were investigated. Two opposite and dose-dependent effects of rLT on normal CFU-GM were found. Low concentrations (5pM) did stimulate the growth, while higher amounts of rLT showed an antiproliferative effect. In contrast, the effect of rTNF was only an inhibition of growth in a dose-dependent fashion. In chronic myeloid leukemia (CML), the CFU-GM was resistant to the growth stimulatory effect of rLT. Furthermore, CML-cells were found to be more susceptible than normal CFU-GM to the antiproliferative effect of both rLT and rTNF. These results show that LT and TNF exhibit qualitative differences in the effects on hematopoietic cells and that CML-cells display an increased susceptibility for the cytostatic effects on LT and TNF.
Gullberg
U
U
Department of Medicine, University of Lund, Sweden.
Nilsson
E
E
D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000473:pathology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor