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Granulocyte-macrophage colony-stimulating factor reactivates fetal
hemoglobin synthesis in erythroblast clones from normal adults
M Gabbianelli, E Pelosi, E Bassano, C Labbaye, S Petti, E Rocca, E Tritarelli, BA Miller, M Valtieri and U Testa
Department of Hematology-Oncology, Istituto Superiore di Sanita Rome,
Italy.
Reactivation of fetal hemoglobin (HbF, alpha 2 gamma 2) synthesis was
previously reported in normal human adult erythroblast colonies ("bursts")
generated by erythroid progenitors (BFU-E) in fetal calf serum-supplemented
(FCS+) semisolid cultures stimulated with erythropoietin (Ep). Our studies
focused on the reactivation of HbF synthesis in normal adult erythroid
bursts generated by peripheral blood mononuclear cells (PBMCs) seeded in
FCS+ methylcellulose culture. Reactivation is almost totally suppressed
when (a) PBMCs are grown in optimized FCS- culture, or (b) PBMCs are first
stringently depleted of monocytes and then plated in FCS+ medium (ie, BFU-E
growth in FCS+ Mo- culture). In both experimental conditions, the
proliferation of lymphocytes and macrophages interspersed among colonies is
drastically reduced, and the cloning efficiency of granulocyte-macrophage
(GM) progenitors is sharply diminished. In either case, addition of
biosynthetic GM colony-stimulating factor (GM-CSF) induces a dose- related
increase of HbF synthesis up to the level in FCS+ culture, with even more
elevated values on delayed addition of Ep. A dose-related increase was also
observed in erythroblast clones generated by highly purified BFU-E. These
results suggest that reactivation of HbF synthesis in normal adults is at
least in part mediated by GM-CSF. Furthermore, they imply intriguing
hypotheses on the mechanism(s) of perinatal Hb switching. Finally, they
raise the possibility of reactivation of HbF synthesis in beta-thalassemia
and sickle cell anemia by GM-CSF therapy.
Volume 74,
Issue 8,
pp. 2657-2667,
12/01/1989
Copyright © 1989 by The American Society of Hematology
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M. Gabbianelli, U. Testa, A. Massa, E. Pelosi, N. M. Sposi, R. Riccioni, L. Luchetti, and C. Peschle
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M Gabbianelli, M Sargiacomo, E Pelosi, U Testa, G Isacchi, and C Peschle
"Pure" human hematopoietic progenitors: permissive action of basic fibroblast growth factor
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September 28, 1990;
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