Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation

Published online November 5, Blood. 2012 Nov 5. [Epub ahead of print] PMID: 23129323 [PubMed - as supplied by publisher] Increased microvessel density contributes to abnormal bone marrow and spleen microenvironment in myelofibrosis (MF). Taking advantage from the JAK2V617F mutation as a marker of malignancy, we investigated, in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons, whether splenic ECs obtained either from capillaries by laser microdissection (LM), or from fresh spleen tissue by cell culture or by cell sorting, harbored such mutation. To extend the analysis to ECs of large vessels, endothelium from the splenic vein was also studied. We found JAK2V617F-positive ECs in 12 out of 18 patients also bearing the mutation in their granulocytes. In 3 patients the mutation was found in at least 2 different EC samples obtained either by LM or cell culture or cell sorting. In 1 out of 6 patients in whom it was searched, the mutation was detected in splenic vein ECs. In conclusion, we provide evidence that a proportion of ECs from the spleen and splenic vein of patients with MF bears the JAK2V617F mutation. We suggest that splenic ECs are involved in the process of malignant transformation in MF.