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Polycythemia vera. II. Hypersensitivity of bone marrow erythroid,
granulocyte-macrophage, and megakaryocyte progenitor cells to interleukin-3
and granulocyte-macrophage colony-stimulating factor
CH Dai, SB Krantz, EN Dessypris, RT Means , ST Horn and HS Gilbert
Department of Medicine, Department of Veterans Affairs Medical Center,
Nashville, TN.
Polycythemia vera (PV) is a clonal disease of the hematopoietic stem cell
characterized by a hyperplasia of marrow erythropoiesis,
granulocytopoiesis, and megakaryocytopoiesis. We previously reported that
highly purified PV blood burst-forming units-erythroid (BFU-E) are
hypersensitive to recombinant human interleukin-3 (rIL-3). Because these
cells may be only a subset, and not representative of marrow progenitors,
we have now studied partially purified marrow hematopoietic progenitor
cells. Dose-response experiments with PV marrow BFU-E showed a 38-fold
increase in sensitivity to rIL-3 and a 4.3-fold increase in sensitivity to
recombinant human erythropoietin (rEpo) compared with normal marrow BFU-E.
In addition, PV marrow colony- forming units-granulocyte-macrophage
(CFU-GM) and CFU-megakaryocyte (CFU-MK) also showed a marked
hypersensitivity to rIL-3 and to human recombinant granulocyte-macrophage
colony-stimulating factor (rGM-CSF). Dose-response curves with rGM-CSF and
blood BFU-E showed a 48-fold increase in sensitivity. No effect of rIL-4,
rIL-6, human recombinant granulocyte-CSF (rG-CSF), or macrophage-CSF
(rM-CSF) was evident, nor was there any effect of PV cell-conditioned
medium on normal BFU-E, when compared with normal cell-conditioned medium.
Autoradiography with 125I-rEpo showed an increase in Epo receptors after
maturation of PV BFU-E to CFU-E similar to that shown with normal BFU-E,
but no increase of specific binding of 125I-rIL-3 by PV CD34+ cells was
seen compared with normal CD34+ cells. These studies show that PV marrow
hematopoietic progenitor cells are hypersensitive to rIL-3 and rGM-CSF,
similar to PV blood BFU-E. While the mechanism does not appear to be due to
enhanced binding of rIL-3, the hypersensitivity of PV progenitor cells to
IL-3 and GM-CSF may be a key factor in the pathogenesis of PV.
Volume 80,
Issue 4,
pp. 891-899,
08/15/1992
Copyright © 1992 by The American Society of Hematology
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