In vitro sensitivity of human erythroid progenitors to hemopoietic growth factors: Studies on primary and secondary polycythemia

Background. Primary proliferative polycythemia is a clonal disease characterized by excessive hemopoiesis and associated with a lower than normal erytropoietin plasma level; in vitro colony studies may reveal increased sensitivity of the abnormal clone to hemopoietic growth factors. Materials and methods. We studied the in vitro formation of erythroid colonies (BFU-E derived clone) in cultures set up with a serum-free medium and containing Epo, interleukin 3 (IL-3) and stem cell factor (SCF), in various combinations. The clonogenic test was performed by plating non adherent mononuclear cells from the peripheral blood of normal subjects and from patients with PPP and secondary polycythemia (SP). Results. SCF is a major amplifier of erythroid colony growth, in the presence of Epo; in cultures from PPP patients, however, the presence of SCF, in addition to Epo, enhances colony formation at about the same rate as in cultures from normal subjects. When SCF is omitted, the presence of even modest amounts of Epo and IL-3 is sufficient to obtain a statisticafiy significant difference between colony formation from PPP patients on the one side, and SP patients and normal subjects on the other. Conclusions. Our results show that in vitro culture studies may contribute an additional diagnostic criterion for distinguishing between PPP and SP in uncertain cases. It is also possible that hypersensitivity to erythropoietic factors may play a role in the pathogenetic mechanism of primary proliferative polycythemia.