Dysregulation of integrin function and induction of inflammation in JAK2-mutated myeloproliferative neoplasia.

An activating point mutation (V617F) of the JAK2-kinase is the molecular hallmark of a group of malignant hematological diseases called polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF). PV, ET and PMF belong to the disease entity of so called chronic myeloproliferative neoplasia (CMN). JAK2V617F-mutated CMN (PV, ET and PMF) is characterized by clonal proliferation of myeloid cells and a striking inflammatory syndrome which is the clinical hallmark of the disease, in particular in advanced phases. Although high pro-inflammatory cytokine levels have been found in the peripheral blood of patients, the cellular and molecular basis of the inflammatory response syndrome is only incompletely understood. Currently, therapeutic options in CMN are limited to symptomatic approaches. In order to develop disease-specific therapies it is of utmost clinical importance and scientific interest to understand the molecular mechanisms of the disease. Therefore, we perform comprehensive in vitro and in vivo investigation of the molecular processes leading to high pro-inflammatory cytokine levels and to inflammation in CMN.