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R Munker and P Koeffler
We investigated the in vitro action of recombinant tumor necrosis factor
alpha (TNF) on the clonal growth of normal and malignant myeloid cells.
Clonogenic cells from six of nine myeloid leukemia cell lines were very
sensitive to the effects of TNF with 50% of the colonies inhibited (ED50)
by concentrations of TNF that ranged between 6 and 150 U/mL. A decrease in
DNA, RNA, and protein synthesis and in cloning efficiency occurred within
three hours of exposure of HL-60 promyelocytes to TNF. The TNF in
combination with recombinant interferons produced an additive or
synergistic inhibition of colony formation of HL-60 and THP-1
myelomonoblasts. Normal human CFU-GM are sensitive to TNF (ED50 between 100
and 50,000 U/mL), but their sensitivity to TNF depends on the source of
colony stimulating factor (CSF) with T lymphocyte derived GM-CSF
(recombinant or natural) partially protecting the CFU-GM from the
suppression exerted by TNF (and interferons). In eight of 15 cases the
clonogenic myeloid leukemia cells from patients with acute or chronic
myeloid leukemia were more sensitive than normal CFU-GM using GM-CSF as a
source of colony stimulating activity. Further studies showed that the
action of TNF on myeloid leukemia cells probably can be only partially
explained by differentiation. Our finding of a possible selective
cytotoxicity to leukemic clonogenic cells by TNF suggests that TNF may have
value in the therapy of some patients with myeloid leukemia.
This article has been cited by other articles:
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| Copyright © 1987 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
