CORRELATION OF GP53 AND P-SELECTIN EXPRESSION IN MYELOPROLIFERATIVE DISORDERS AND NORMAL CONTROLS

Platelet degranulation occurs when platelets are activated Alpha degra nulation releases P-selectin whereas lysosomal degranulation releases GP53. A correlation between these two markers might therefore be expec ted. We studied the correlation between P-selectin and GP53 in 50 pati ents with myeloproliferative disorders (MPD), 35 normal controls and 1 05 disease controls (patients with inflammatory bowel disease [IBD, n= 52], rheumatoid arthritis [RA, n=26] and coronary artery disease [CAD, n=27]) by flow cytometry before and after stimulation with thrombin e x vivo. There was no significant correlation between percentage expres sion of P-selectin and GP53 in unstimulated samples in normal individu als; r=0.13, P=0.3, n=34. Mild thrombin stimulation (10 mU/ml) led to both alpha and lysosomal degranulation with a strong correlation (r=0. 62, P<0.001, n=35). Disease controls (IBD, RA and CAD) showed similar trends. In patients with MPD, in contrast, a strong correlation betwee n the expression of these platelet activation markers was demonstrable in unstimulated samples (r=0.37, P=0.007, n=50). P-selectin and GP53 expression in stimulated samples also correlated well. The data suppor t the existence of different control pathways for the steady state exp ression of P-selectin and GP53. Heterogeneous steady state responses o f P-selectin and GP53 may be physiological and loss of this heterogene ity may be a hitherto unreported and pathologically important feature of MPD. This lack of correlation appears to be specific to MPD and is not simply a function of increased in vivo platelet activation.