PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemiaAn increased incidence of thrombosis, both arterial and venous, has been reported in essential thrombocythaemia (ET) (Spivak et al, 2003). ET is considered as a 'clonal' myeloproliferative disorder, but studies of X-chromosome inactivation pattern (XCIP) indicated that a proportion of patients with ET, diagnosed according to the currently available criteria, presented polyclonal myelopoiesis (el-Kassar et al, 1997;Harrison et al, 1999a;Chiusolo et al, 2001;Shih et al, 2001Shih et al, , 2002. Since the rate of thrombosis in patients with polyclonal myelopoiesis was significantly lower than in monoclonal patients (Harrison et al, 1999a;Chiusolo et al, 2001;Shih et al, 2002), assessment of clonality would enable the identification of patients within different risk categories suitable for risk-adapted treatment strategies . However, beyond concerns as a result of age-dependent unbalanced X-chromosome skewing (Champion et al, 1997;Mitterbauer et al, 1999), the major limitation of XCIP analysis is that it can be performed only in women.No specific molecular marker of ET has been identified yet, although a number of cellular and molecular abnormalities have been described (Spivak et al, 2003); these include reduced platelet content of Mpl, the receptor for thrombopoietin (Horikawa et al, 1997;Harrison et al, 1999b;Li et al, 2000), spontaneous in vitro growth of erythroid progenitors (endogenous erythroid colonies, EEC) (Prchal & Axelrad, 1974;Kralovics et al, 2003) and overexpression of the PRV-1 gene (Teofili et al, 2002a;Johansson et al, 2003a;Liu et al, 2003;Tefferi et al, 2004). However, an association between these abnormalities and thrombosis has been reported only occasionally (Teofili et al, 2002b;Johansson et al, 2003b).The aim of this study was to assess whether any of these three epigenetic markers clustered with clonality status in females with ET; if so, it (they) might be considered to represent (a) 'surrogate marker(s)' of clonality and, possibly, of thrombotic risk.
Patients and methodsOne hundred females with ET were studied; they comprised an unselected consecutive population of patients who attended the outpatient departments of our Haematology institutions for either diagnostic or routine follow-up purposes. Diagnosis
SummaryFemales with the monoclonal type of essential thrombocythaemia (ET), based on the X-chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV-1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty-three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P ¼ 0AE009). The frequency of abnormalities of PRV-1, EEC, or Mpl was similar in monoclonal and polyclonal su...