POLYCYTHEMIA-VERA .5. ENHANCED PROLIFERATION AND PHOSPHORYLATION DUE TO VANADATE ARE DIMINISHED IN POLYCYTHEMIA-VERA ERYTHROID PROGENITOR CELLS - A POSSIBLE DEFECT OF PHOSPHATASE-ACTIVITY IN POLYCYTHEMIA-VERA

Erythropoietin (EP) and stem cell factor (SCF), are essential growth f actors for erythroid progenitor cell proliferation and differentiation in serum-free culture, It has been previously shown that burst-formin g units-erythroid and colony-forming units-erythroid from patients wit h polycythemia vera (PV) have enhanced sensitivity to EP and SCF compa red with normal erythroid progenitors, but little is known about the m echanism for this difference, In the present investigation, the effect of EP and SCF on protein tyrosine phosphorylation in day-8 normal and PV erythroid colony-forming cells, which give rise to colonies of 2-4 9 hemoglobinized cells, was studied, EP rapidly induced tyrosine phosp horylation of the EP receptor, whereas the most prominent phosphorylat ed protein induced by SCF was identified as the SCF receptor, No addit ional phosphorylated proteins were evident when PV cells were compared with normal cells. Culture of normal erythroid progenitors with ortho vanadate, an inhibitor of protein tyrosine phosphatases, resulted in a n increased number of erythroid colonies and enhanced protein tyrosine phosphorylation, However, in contrast, little enhancement was evident with PV cells. These results indicate that, although vanadate may be acting in normal erythroid progenitors as a phosphatase inhibitor that potentiates the kinase activity induced by SCF and EP, this function is diminished in PV cells. Because erythropoiesis is regulated by a ba lance between protein tyrosine kinase activity and protein tyrosine ph osphatase activity, PV patients may have an abnormal phosphatase activ ity allowing increased cell proliferation. (C) 1997 by The American So ciety of Hematology.