Early progenitor cells from human mobilized peripheral blood express low levels of the flt3 receptor, but exhibit various biological responses to flt3-L.
The biological effects of flt3-L, and the expression of its tyrosine kinase receptor (flt3, CD135) were investigated on the immature subsets of human circulating peripheral blood progenitors obtained from cancer patients or normal volunteer donors, after mobilization with rhG-CSF or chemotherapy. flt3 was expressed at low levels, and its expression increased concomitantly with expression of CD38 within the CD34+ cell population. Despite this low-level expression, flt3-L exerted synergistic effects with a combination of c-kit ligand, IL-3, IL-6, GM-CSF and G-CSF, mainly to induce proliferation of CD34+/CD38- cells. In addition, flt3-L increased the detection of HPP-CFC, both immediately after cell selection, and after 7 and 14 d of cultures. We conclude that flt3-L is active on circulating early mobilized haemopoietic progenitors, despite the low- level expression of its receptor.
Aurran-Schleinitz
T
T
Laboratoire de Biologie Cellulaire, Centre de Thérapie Cellulaire, Institut Paoli-Calmettes, Centre Régional de Lutte Contre le Cancer Provence Alpes-Côte d'Azur, Marseille, France.
Imbert
A M
AM
Humeau
L
L
Bardin
F
F
Charbord
P
P
Chabannon
C
C
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival; D005434:Flow Cytometry; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D009244:NAD+ Nucleosidase; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084881:flt3 ligand protein; D020794:Receptor Protein-Tyrosine Kinases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1