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S Saeland, C Caux, C Favre, JP Aubry, P Mannoni, MJ Pebusque, O Gentilhomme, T Otsuka, T Yokota and N Arai
UNICET Laboratory for Immunological Research, Dardilly, France.
Induction of proliferation and differentiation in response to recombinant
human interleukin-3 (hIL-3) was studied in liquid and semisolid cultures of
umbilical cord blood and bone marrow cells that were fractionated by
"panning" with anti-My10 antibody according to expression of CD34 antigen.
Cells from enriched fractions (70% to 90% CD34+) were found to proliferate
strongly in response to hIL-3. Phenotypic analysis and morphologic
characterization of the proliferating cells demonstrated a rapid decrease
in CD34+ cells and an exponential increase in the number of cells belonging
to the neutrophilic, eosinophilic, monocyte/macrophage, and thrombocytic
lineages. When combined with recombinant human erythropoietin, burst
colonies and cells expressing glycophorin-A were detected, thereby
demonstrating the effects of hIL-3 on erythroid progenitors. Further, the
development of mixed-erythroid colonies indicated that multipotential cells
within CD34-enriched fractions responded to hIL-3. In addition, we examined
the effect of hIL-3 on the proliferation of primary acute myeloblastic
leukemia cells in liquid culture. We found that hIL-3 was able to induce
cell proliferation in a proportion of the cases tested. Heterogeneity of
the responses to hIL-3 was in part related to French-American-British
classification but could not be correlated with CD34 antigen expression by
the leukemic cells. These results indicate that, although the effects of
hIL-3 on proliferation and differentiation of cells obtained from normal
hematopoietic specimens were primarily borne by CD34+ cells, expression of
the CD34 molecule per se is an insufficient condition to determine a growth
response to this lymphokine.
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