The presence of JAK2V617F mutation in the liver endothelial cells of patients with Budd-Chiari syndrome

Abstract

Patients with myeloproliferative disorders are at a high risk of developing thrombotic events. Several investigators have hypothesized that endothelial cell (EC) abnormalities might contribute to this prothrombotic state. Budd-Chiari syndrome (BCS) and portal vein thrombosis have been reported to be associated with JAK2V617F-positive hematopoiesis. We explored whether JAK2V617F was present in ECs in the vessels of polycythemia vera (PV) patients with BCS using laser capture microdissection followed by nested polymerase chain reaction or reverse-transcribed polymerase chain reaction. The ECs of the 2 BCS patients with PV were homozygous for the JAK2V617F and were shown to express transcripts characteristic of ECs but not hematopoietic cells. ECs of the other BCS patient with PV and 2 patients with hepatoportal sclerosis without PV contained exclusively wild-type JAK2. The presence of JAK2V617F in both ECs and hematopoietic cells belonging to BCS patients with PV indicate that ECs in PV are involved by the malignant process and that in a subpopulation of the patients the disease might originate from a common cell of origin for hematopoietic and ECs.