Therapeutic implications of serum factors inhibiting proliferation and inducing differentiation of myeloid leukemic cells

M. A.S. Moore, J. Gabrilove, A. P. Sheridan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Murine post-endotoxin sera contain high levels of myeloid colony-stimulating factor(s) (GM-CSF) and factors capable of inducing terminal granulocyte and macrophage differentiation of the murine myelomonocytic leukemic cell line WEHI-3. The combination of C. parvum and endotoxin induced a serum activity capable of inducing tumor necrosis and inhibiting leukemic colony formation in vitro. This factor (TNF) could be separated from the differentiation-inducing factor (GM-DF) and from CSF. In conjuction with a Phase I trial of highly purified endotoxin in patients with advanced malignancy, we monitored human post-endotoxin sera for CSF and GM-DF. Induction of GM-DF occurred maximally at 2-6 h and was associated with increased serum levels of CSF active against the patient's own bone marrow. Following repeated injections of escalating doses of endotoxin, persistent levels of GM-DF were detected both pre-endotoxin and 24 h post-endotoxin treatment. The ability to induce repeatedly a serum protein with potent capacity to promote terminal differentiation of myelomonocytic leukemic cells suggests a possible therapeutic role in human myeloid leukemias.

Original languageEnglish
Pages (from-to)125-137
Number of pages13
JournalBlood Cells
Volume9
Issue number1
StatePublished - 1983
Externally publishedYes

Fingerprint

Dive into the research topics of 'Therapeutic implications of serum factors inhibiting proliferation and inducing differentiation of myeloid leukemic cells'. Together they form a unique fingerprint.

Cite this