The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils of polycythemia vera.

BACKGROUND: The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes. DESIGN AND METHODS: We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63(+) basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor. RESULTS: We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63(+) basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63(+) basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden. CONCLUSIONS: These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus

The GINGER Project and status of the ring-laser of LNGS

A ring-laser attached to the Earth measures the absolute angular velocity of the Earth summed to the relativistic precessions, de Sitter and Lense-Thirring. GINGER (Gyroscopes IN GEneral Relativity) is a project aiming at measuring the LenseThirring effect with a ground based detector; it is based on an array of ring-lasers. Comparing the Earth angular velocity measured by IERS and the measurement done with the GINGER array, the Lense-Thirring effect can be evaluated. Compared to the existing space experiments, GINGER provides a local measurement, not the averaged value and it is unnecessary to model the gravitational field. It is a proposal, but it is not far from being a reality. In fact the GrossRing G of the Geodesy Observatory of Wettzell has a sensitivity very close to the necessary one. G ofWettzell is part of the IERS system which provides the measure of the Length Of the DAY (LOD); G provides information on the fast component of LOD. In the last few years, a roadmap toward GINGER has been outlined. The experiment G-GranSasso, financed by the INFN Commission II, is developing instrumentations and tests along the roadmap of GINGER. In this short paper the main activities of G-GranSasso and some results will be presented. The first results of GINGERino will be reported, GINGERino is the large ring-laser installed inside LNGS and now in the commissioning phase. Ring-lasers provide as well important informations for geophysics, in particular the rotational seismology, which is an emerging field of science. GINGERino is one of the three experiments of common interest between INFN and INGV