In vitro suppression of normal granulocytic stem cells by inhibitory activity derived from human leukemia cells

Hal Broxmeyer, N. Jacobsen, J. Kurland, N. Mendelsohn, A. S. Moore

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Abstract

Extracts and conditioned medium of bone marrow and blood cells from patients with acute leukemia were assayed for activity against granulocyte-monocyte colony-forming cells in agar (CFU-C). Cell extracts from 76 of 85 patients reproducibly inhibited colony formation of normal CFU-C by 28-90%. Leukemia cell-derived inhibitory activity (LIA) was at a maximum in medium conditioned for 3-4 days with leukemia cells. LIA was against CFU-C during S-phase and had no influence on production of colony-stimulating activity (CSA) by CSA-producing cells. No evidence of CSA inactivation was obtained. LIA was thus different from the previously reported PMN-derived inhibitory activity which only inhibits CSA production. Most of the crude LIA was lost at 37° C within 5 hours, but 10 minutes of incubation with CFU-C resulted in maximum inhibition. Size and cell morphology of colonies surviving LIA were not influenced. Inhibition of CFU-C by leukemia cell extract was observed after 6-8 days but not after 14 days of incubation. Velocity sedimentation experiments demonstrated that this observation was not due to a reversible effect on sensitive CFU-C. Colonies scored after 14 days were derived from CFU-C not sensitive at the time of treatment but were inhibited by multiple additions of leukemia cell extract. Human marrow cells that form granulocyte colonies in fibrin clot diffusion chambers in mice and pre-CFU-C in suspension culture in vitro were not inhibited by single and multiple additions of leukemia cell extract. Extracts from normal hematopoietic cells did not inhibit exogenously stimulated colony formation. The results suggest that inhibition was not nonspecifically toxic and may explain suppression of normal hematopoiesis associated with acute leukemia.

Original languageEnglish (US)
Pages (from-to)497-511
Number of pages15
JournalJournal of the National Cancer Institute
Volume60
Issue number3
StatePublished - 1978
Externally publishedYes

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Human Activities
Leukemia
Stem Cells
Cell Extracts
Conditioned Culture Medium
Granulocytes
Poisons
Hematopoiesis
In Vitro Techniques
Fibrin
S Phase
Cell Size
Bone Marrow Cells
Agar
Monocytes
Blood Cells
Suspensions
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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In vitro suppression of normal granulocytic stem cells by inhibitory activity derived from human leukemia cells. / Broxmeyer, Hal; Jacobsen, N.; Kurland, J.; Mendelsohn, N.; Moore, A. S.

In: Journal of the National Cancer Institute, Vol. 60, No. 3, 1978, p. 497-511.

Research output: Contribution to journalArticle

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