Erythroid colony formation by polycythemia vera bone marrow in vitro. Dependence on erythropoietin.

Abstract

A B S T R A C T In the plasma clot culture system, both normal and polycythemia vera (PV) bone marrow cells respond to erythropoietin (Ep), giving rise to large numbers of colonies of erythroid cells. In PV, but not in normal individuals, the marrow produced endogenous erythroid colonies (EEC) in the absence of exogenous Ep. The number of EEC formed varied from patient to patient comprising anywhere from 6 to 29% of the total number of colonies formed in the presence of Ep. Exposure, before use in culture, of fetal calf serum and citrated bovine plasma to the gammaglobulin fraction of rabbit anti-Ep serum followed by treatment with goat anti-rabbit gamma-globulin resulted in a significant decrease in EEC formation. Addition of anti-Ep directly to the culture medium produced similar results. In addition, the production of EEC in response to added Ep was inhibited in the presence of anti-Ep. Addition of very small doses of highly purified Ep to anti-Ep-treated cultures resulted in the reappearance of a significant number of EEC. These results suggest that EEC formation in PV may be due to a population of erythroid-committed precursors that are abnormally sensitive to small concentrations of Ep which may be present in fetal calf serum and citrated plasma. Although the mechanism of formation of these cells is not known, it appears that the final steps in the formation of red cells derived from this clone of precursors is subject to the usual Ep control.

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

“…Erythropoietin (Ep). Urinary excretion and plasma concentration of Ep were assayed by the technique of 59Fe incorporation in polycythemic (exhypoxic) mice (14). The amount of Ep in each sample was determined by observing its effect on 10-15 mice.…”

JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials

“…Early studies showed that erythropoiesis in PV patients was hypersensitive to erythropoietin (Epo), 1,2 and possibly independent of this cytokine. 3,4 Culture of PV bone marrow cells produced colony forming unit-derived erythroid colonies in the absence of Epo, termed endogenous erythroid colonies (EEC), that were 9-37% of the erythroid colony number obtained in the presence of Epo.…”

Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms

“…1,2 Patients with MPNs have an increased risk of thrombotic and bleeding complications and disease progression to acute myeloid leukemia. Currently, the treatment of MPNs involves the palliative use of cytoreductive agents.…”