POSSIBLE INVOLVEMENT OF PROTEIN-KINASE-C IN THE ABERRANT REGULATION OF ERYTHROPOIESIS IN POLYCYTHEMIA-VERA

To examine the possible involvement of protein kinase C (PKC) in the r egulation of aberrant erythropoiesis of polycythemia vera (PV), we inv estigated the effects of PKC inhibitors on in vitro burst-forming unit of erythroid (BFU-E)-derived colony formation by bone marrow (BM) and peripheral blood (PB) cells obtained from five PV patients. 1-(Isoqui noline-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibito r of PKC, suppressed the colony formation by BM and PB cells of PV pat ients in a dose-dependent manner, similar to those in the normal indiv iduals. However, the 50% inhibitory concentrations (IC50) of H-7 in PV BM and PB cells were significantly higher than those in normal BM and PB cells, respectively. The BFU-E-derived colony formation by PV BM a nd PB cells was also less affected by Staurosporine, another PKC inhib itor, than those in a normal subject. Furthermore, in the study of PV, the IC50 of endogenous colonies formed in the absence of erythropoiet in was much higher than that of colonies formed by the stimulation of erythropoietin. By contrast, N-(2-guanidinoethyl)-5-isoquinolinesulfon amide dihydrochloride (HA1004), a cyclic AMP-dependent kinase inhibito r, did not have such inhibitory effects. These findings suggest that P KC, as a second messenger, is involved in the regulation of aberrant e rythropoiesis of PV. (C) 1997 Elsevier Science Ltd.