Sequencing_of_JAK2V617F_MPN_Mouse_tumours

A gain-of-function JAK2V617F mutation is found in the vast majority of patients with polycythemia vera (PV) and in 50-60% of those with essential thrombocythemia (ET) or idiopathic myelofibrosis (IMF) IMF. We have generated a conditional knock-in mouse in which human JAK2V617F is expressed under the control of the mouse Jak2 locus. The mice developed modest increases in hemoglobin and platelet levels reminiscent of human JAK2V617F-positive ET. Like patient with ET, ~2% of which progress to PV, 5-10% of the ET-like mice developed PV-like phenotypes overtime. The PV-like phenotype in the transformed PV-like mice is transplantable and is associated with severe extramedullary erythropoiesis in spleen and/or liver. In order to identify the cooperating mutations involved in the disease transformation, exome sequencing was carried out on samples of spleen or liver from the transformed mice as well as their constitutive samples (i.e. tail or peripheral blood pre-transformation).