PRV-1 mRNA expression discriminates two types of essential thrombocythemia

Essential thrombocythemia (ET) is a heterogeneous disorder. For example, the growth of erythropoietin-independent erythroid colonies, termed endogenous erythroid colonies (EECs), has previously been observed in only 50% of ET patients. We have recently described the overexpression of a hematopoietic receptor, PRV-1 (polycythemia rubra vera-1), in patients with polycythemia vera (PV). Here, we compare PRV-1 expression and EEC formation in a cohort of 30 patients with ET; 50% of the ET patients in our cohort displayed EEC growth. Likewise, 50% of the ET patients overexpressed PRV-1. Remarkably, only the 15 ET patients displaying EEC growth showed elevated PRV-1 expression, while the 15 EEC-negative ET patients expressed normal PRV-1 levels. It has previously been reported that EEC-positive ET patients develop PV during long-term follow-up. Here, we show that 40% of the PRV-1-positive patients develop symptoms of PV during the course of their disease. In contrast, none of the 15 PRV-1-negative patients displayed such symptoms (p=0.017). Moreover, PRV-1-positive patients had a significantly higher number of thromboembolic or microcirculatory events (p=0.003). We propose that PRV-1-positive ET comprise a pathophysiologically distinct subgroup of patients, one that is at risk for the development of complications and for the emergence of PV.This work was supported by the Alfried Kupp Förderpreis für Junge Hochschullehrer, the Else Kröner-Fresenius-Stiftung and the SFB 364, TP A12, granted to H. L. P. as well as by the German Kompetenznetz Acute and Chronic Leukemias (Project 25)