In vitro purging of clonogenic leukaemic cells from human bone marrow by interferon-gamma-activated monocytes.
With a view to the immunologically mediated purging of autologous bone marrow transplants in acute myeloid leukaemia, the efficacy of cytotoxic monocytes to eradicate leukaemic cells has been studied using clonogenic assays. U937 cells were found to be sensitive to highly purified and interferon-gamma-activated human monocytes whereas HL60 cells were rather resistant as measured in an MTT-based cytotoxicity assay under liquid conditions. A spectrophotometric clonogenic assay measured almost complete inhibition of clonogenic activity for U937 cells at low effector-to-target cell (E/T) ratios of at least 0.1. Limiting dilution analysis detected a 2-3 log10 unit reduction in clonogenic activity. In an experimental mixture of U937 cells with a 20-fold excess of normal bone marrow nuclear cells a maximum 2-log10-unit killing could be measured at E/T = 10. Only at high E/T ratios could a reduction in granulocyte/macrophage-colony-forming units (cfu) be observed with only marginal effects on erythroid cfu and erythroid burst-forming. In conclusion, cytotoxic monocytes are highly potent anti-leukaemic effector cells, as measured in clonogenic assays, that do not compromise normal human progenitors.
van de Loosdrecht
A A
AA
Department of Hematology, Academisch Ziekenhuis, Vrije Universiteit, Amsterdam, The Netherlands.
Ossenkoppele
G J
GJ
Beelen
R H
RH
Broekhoven
M G
MG
Schweitzer
K M
KM
Langenhuijsen
M M
MM
D000208:Acute Disease; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D009000:Monocytes / Q000276:immunology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D011994:Recombinant Proteins