Objective. To elucidate the mechanism of immunologic escape of leukemia cel
ls and establish an effective anti-leukemia immunotherapy, we attempted to
generate dendritic cells from leukemia cells in patients with acute myeloge
nous leukemia (AML). Using these leukemia-derived dendritic cells, we inves
tigated leukemia cell-associated T-cell anergy.
Materials and Methods. Leukemia cells of 30 patients with AML were cultured
with granulocyte-macrophage colony-stimulating factor, interleukin-4, and
tumor necrosis factor-alpha. Cultured leukemia cells were evaluated for ant
igen-presenting ability by mixed leukocyte culture (MLC). Normal lymphocyte
s, which were cocultured with leukemia blasts in the first MLC, were cultur
ed with leukemia-derived dendritic cells in the second MLC.
Results. In cultures of leukemia cells from 21 of 30 patients examined, cel
ls with stellate morphology and cell fractions with CD1a(+) and/or CD83(+)
were present. Autologous MLC using lymphocytes obtained in remission phase
as responders as well as allogeneic MLC demonstrated antigen-presenting abi
lity in leukemia-derived dendritic cells. Leukemia cells of FAB-M0, M1, M2,
M3, or M6 morphology/phenotype gave rise to dendritic cells as well as leu
kemia cells of M5. The leukemic origin of dendritic cells was suggested by
in situ hybridization. By coculture with CD80- leukemia blasts, the respons
e of normal lymphocytes to leukemia-derived dendritic cells cultured from t
he same individual as that of leukemia blasts was markedly reduced, compare
d with the lymphocytes cultured with leukemia blasts from a different indiv
idual as leukemia blasts.
Conclusions. Escape of leukemia cells from anti-leukemia immunity may be as
sociated with T-cell anergy caused by leukemia blasts. The results of the p
resent study suggest that leukemia-derived dendritic cells can be applied e
fficiently in anti-leukemia immunotherapy. (C) 2001 International Society f
or Experimenta. Hematology. Published by Elsevier Science Inc.