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Circulating erythroid progenitors in polycythemia vera are hypersensitive
to insulin-like growth factor-1 in vitro: studies in an improved serum-free
medium [see comments]
PN Correa, D Eskinazi and AA Axelrad
Department of Anatomy and Cell Biology, Faculty of Medicine, University of
Toronto, Ontario, Canada.
We have investigated the question of erythropoietin (Epo) hypersensitivity
versus Epo independence as the basis for the endogenous erythroid bursts
(EEBs) that develop in cultures without added Epo from hematopoietic cells
of polycythemia vera (PV) patients. Using an improved serum-free (SF)
medium containing interleukin (IL)-3, but no insulin-like growth factor-1
(IGF-1), and devoid of contaminants that influence erythropoiesis, we
compared circulating normal and PV early erythroid progenitors (BFU-E) with
respect to their responses in vitro to recombinant human (rHu) Epo.
Cultures were seeded with Ficoll- Hypaque density-separated peripheral
blood (PB) mononuclear cells (MNCs), and erythroid bursts, together with
their component colonies of > or = 50 cells, were scored in situ at 13
to 16 days of culture. The Epo dose-response curve of BFU-E from PV
patients was found to be statistically indistinguishable from that of
normal subjects. This observation provides compelling evidence against the
Epo- hypersensitivity hypothesis. In the complete SF medium minus Epo, the
sensitivity of BFU-E to IGF-1 was much greater in PV than in normals, the
dose-response curve being shifted to the left by at least 2 orders of
magnitude. These data show that the erythroid progenitor cell response in
PV is hypersensitive to IGF-1, and independent of Epo. The data also
emphasize the importance of truly SF medium conditions for assessment of
progenitor cell sensitivities to recombinant growth factors. Depletion of
adherent cells totally prevented erythroid burst formation by normal
circulating progenitors, but did not prevent the hypersensitive response to
IGF-1 of such cells from PV patients. Hence, again unlike its normal
counterpart, the progenitor cell response in PV appears to be independent
of adherent cell control.
Volume 83,
Issue 1,
pp. 99-112,
01/01/1994
Copyright © 1994 by The American Society of Hematology
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