Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells

Hal Broxmeyer, Scott Cooper, Li Lu, Giao Hangoc, Dirk Anderson, David Cosman, Stewart D. Lyman, Douglas E. Williams

Research output: Contribution to journalArticle

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Abstract

Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte-macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhulL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhulL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34+++HLA-DR andCD34+++HLA-DR+CD33- sorted cells in which ≥ 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

Original languageEnglish
Pages (from-to)2142-2149
Number of pages8
JournalBlood
Volume77
Issue number10
StatePublished - May 15 1991

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Erythroid Precursor Cells
Stem Cell Factor
Proto-Oncogenes
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Erythropoietin
Bone Marrow
Ligands
Granulocyte-Macrophage Progenitor Cells
Bone
Megakaryocytes
Granulocytes
HLA-DR Antigens
Monocytes
Cells
Cytokines
Macrophages
Interleukin-3
Assays
Stem Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Broxmeyer, H., Cooper, S., Lu, L., Hangoc, G., Anderson, D., Cosman, D., ... Williams, D. E. (1991). Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. Blood, 77(10), 2142-2149.

Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. / Broxmeyer, Hal; Cooper, Scott; Lu, Li; Hangoc, Giao; Anderson, Dirk; Cosman, David; Lyman, Stewart D.; Williams, Douglas E.

In: Blood, Vol. 77, No. 10, 15.05.1991, p. 2142-2149.

Research output: Contribution to journalArticle

Broxmeyer, H, Cooper, S, Lu, L, Hangoc, G, Anderson, D, Cosman, D, Lyman, SD & Williams, DE 1991, 'Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells', Blood, vol. 77, no. 10, pp. 2142-2149.
Broxmeyer, Hal ; Cooper, Scott ; Lu, Li ; Hangoc, Giao ; Anderson, Dirk ; Cosman, David ; Lyman, Stewart D. ; Williams, Douglas E. / Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. In: Blood. 1991 ; Vol. 77, No. 10. pp. 2142-2149.
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N2 - Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte-macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhulL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhulL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34+++HLA-DR andCD34+++HLA-DR+CD33- sorted cells in which ≥ 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

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