Increased risk for vascular complications in PRV‐1 positive patients with essential thrombocythaemia

Abstract

Summary. Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant (P ¼ 0AE02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients (P ¼ 0AE03). The time from diagnosis of ET to the requirement of plateletlowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients (P ¼ 0AE014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for plateletlowering therapy, compared with PRV-1 negative ET patients.

Initial (Latent) Polycythemia vera with Thrombocytosis Mimicking Essential Thrombocythemia

“…Moreover, in a considerable number of patients with ET a significant association between a low erythropoietin level and an elevated PVR-1 gene expression was described [36]. Although the occurrence of this concurrent marker profile was recognized to a far lesser degree in other series [37, 38], it has been suggested that two types of ET may be distinguished [35, 39] and that PVR-1-positive ET reveals a higher risk for vascular complications [40]. However, in contrast to the elaborate cell culture studies and molecular biological methods applied in these cases, descriptions of BM features were mostly lacking or nonspecific.…”

The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients

“…10 In our model, EEC/PRV-1-positive ET and IMF patients are molecularly and clinically more similar to PV patients than to other patients who carry the same clinically defined diagnosis. [9][10][11] The recent description of a point mutation in the Janus kinase 2 (Jak2; Jak2V617F) in the majority of patients with PV as well as subgroups of patients with ET and IMF [12][13][14] allows us to correlate the presence of this mutation with the occurrence of other markers in individual patients. This analysis can refute or prove the hypothesis that EEC/PRV-1-positive MPD patients share a common molecular determinant of disease etiology.…”

Usefulness of the quantitative assessment of PRV-1 gene expression for the diagnosis of polycythemia vera and essential thrombocythemia patients

“…We and most others have used purified granulocytes; 2 groups have analyzed total blood leukocytes, likewise reasoning that this would be more applicable to the routine diagnostic setting. 3,4,8 Because PRV-1 expression is restricted to the granulocytic lineage and its expression is determined relative to a housekeeping gene, the choice of cell population assayed can alter the result.…”

“…In the 6 studies in which ET patients were analyzed, 4 different housekeeping genes were used (GAPDH, GUS, beta-2-microglobulin, and RPL19). [1][2][3][4][5][6]8 The present study adds a fifth, c-abl. This methodological difference may be important in combination with a second variance, the cell population assayed.…”

“…The data presented by Cilloni et al differ from ours and other previous reports in that they find PRV-1 overexpression in all ET patients tested, whereas we and others find it only in a subset of patients. [1][2][3][4][5][6]8 In this context, 2 aspects are essential: methodological details of the assay and the cell population assayed. In the 6 studies in which ET patients were analyzed, 4 different housekeeping genes were used (GAPDH, GUS, beta-2-microglobulin, and RPL19).…”