Research Seminar: A JAK of all trades? New insights into the initiation and pathology of the myeloproliferative neoplasms.

Professor Ian Hitchcock, Department of Biology, University of York

Tuesday 14th November, 1.00 p.m., Stacey Lecture Theatre 1

A somatic mutation in Janus kinase 2 (JAK2 V617F) is responsible for the vast majority of Philadelphia Chromosome-negative myeloproliferative neoplasms (MPNs); a diverse group of haematological malignancies characterised by increases in erythrocytes and platelets. Despite the function of this mutation having been studied extensively since its discovery in 2005, its mechanisms of activation and diverse pathology it causes, remains somewhat elusive. We have recently demonstrated that the thrombopoietin receptor, MPL, is essential for JAK2 V617F-driven disease development, and, using single molecule imaging techniques, now have evidence of an entirely novel mechanistic paradigm for activation of the oncogene. Furthermore, we are studying the effect of JAK2 V617F on endothelial function, highlighting a potential chronic inflammatory phenotype which may influence the clonal expansion of malignant haematopoietic stem and progenitor cells.