Polycythaemia vera: in vitro studies of circulating erythroid progenitors.

Abstract

Summary.Peripheral blood mononuclear cells from healthy subjects, patients with secondary polycythaemia and patients with polycythaemia vera (PV) were cultured using the plasma clot technique, and large erythroid colonies or bursts were scored after 14 d. Erythroid bursts appeared without addition of erythropoietin in all 20 patients with PV but never in normal subjects (n=10) nor in patients with secondary polycythaemia (n=6). The erythropoietin dose‐response curves in six PV patients were characterized by an initial plateau followed by a nearly normal response. This suggests the coexistence of two populations of erythroid progenitors in PV, one abnormally sensitive, the other normally responsive to erythropoietin. In nine patients the ratio of spontaneous bursts to bursts induced by high doses of erythropoietin from the blood on day 14 was identical with the ratio of spontaneous colonies to colonies induced by high doses of erythropoietin from the bone marrow of the same patients on day 7. This argues against the hypothesis that spontaneous erythroid bursts are derived from erythroid progenitors (BFUE) abnormally sensitive to erythropoietin. Moreover blood mononuclear cells from healthy subjects were found to give rise to erythroid bursts when erythropoietin addition was delayed until 6 d in culture. This is consistent with the concept that erythropoietin is not normally required in vivo for the differentiation of early (BFUE) to late (CFUE) erythroid progenitors. These findings suggest that in PV all BFUE are normally responsive to the physiological factor(s) different from erythropoietin and responsible for their differentiation into CFUE, and that the abnormal response to erythropoietin, distinctive of a population of erythroid progenitors, is expressed only at the most mature (CFUE) level.