GM-CSF-mediated proliferation induction improves the susceptibility of leukemia cells to lymphokine-activated killer cells.
Our studies on the susceptibility of fresh noncultured leukemia cells to interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells have shown that about two thirds of the leukemias are susceptible to the LAK-cell-mediated cytolysis. Analysis of 214 acute leukemias revealed considerable variation in the degree of cytotoxicity achieved. Cytolysis was substantially lower in fresh noncultured acute leukemia samples than in K562 and Daudi cell lines (mean Cr-release 21.0 +/- 16.0% versus 69.2 +/- 6.6% and 70.8 +/- 7.9%). Augmentation of susceptibility to LAK-cell lysis is desirable in connection with therapeutic application of IL-2-induced effector mechanisms. We observed a relationship between the LAK-cell susceptibility of leukemia cells and their spontaneous proliferation rate, which is significantly higher in LAK-cell-sensitive than in LAK-cell-resistant leukemias. It was therefore considered useful to examine the possibility of augmenting LAK-cell sensitivity by proliferation induction. These studies demonstrate that incubation of blast cells from acute myeloid leukemia (AML) and chronic myelogenous leukemia in myeloid blast crisis (CML-BC) with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) significantly augments LAK-cell susceptibility and that this is associated with an increased cell proliferation.
Teichmann
J V
JV
Department of Hematology and Oncology, Universitaetsklinikum Steglitz, Free University of Berlin, Germany.
Ludwig
W D
WD
Thiel
E
E
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007938:Leukemia / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D013268:Stimulation, Chemical
D016178:Granulocyte-Macrophage Colony-Stimulating Factor