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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. IntroductionPolycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative disorder (MPD) that is associated with mutations of a cytosolic tyrosine kinase, JAK2. 1,2 A gain-of-function mutation (JAK2V617F) is present in more than 90% of patients with PV. 1,2 PV has been associated with the intraabdominal thromboses. 3 Some persons with normal blood counts who develop splanchnic vein thrombosis, including Budd-Chiari syndrome (BCS) and portal vein thrombosis, have been reported to have JAK2V617F-positive hematopoiesis, indicating that this thrombotic tendency may precede the development of an MPD. 4,5 During early mammalian development, a common cell of origin for hematopoietic and endothelial cell (EC) elements has been identified. [6][7][8] This so-called hemangioblast has been characterized in adults, but its role in normal hematopoiesis or the pathogenesis of the MPDs remains poorly defined. 9,10 Since 1997, postnatal vasculogenesis has been proposed to involve a hierarchy of circulating endothelial progenitor cells. 11 Some of these endothelial progenitor cells are of myeloid origin, whereas others have a more robust proliferative potential and are solely of EC origin. 12,13 Involvement of endothelial progenitor cells by JAK2V617F has been studied by several groups. 12,14,15 Vascular endothelium provides a nonadhesive surface to circulating neutrophils and platelets while helping to prevent blood clotting. Several groups have hypothesized that EC dysfunction might contribute to the hypercoagulable state associated with PV by orchestrating the recruitment of blood cell elements to sites of injury or by regulating vascular tone by impairing the release of nitric oxide. [16][17][18] To further explore the origins of ECs in MPD, we examined whether ECs in nonhematopoietic organs harbored JAK2V617F. We tested this hypothesis by studying ECs in venules of liver biopsy specimens obtained from patients with BCS and PV using laser capture microdissection (LCM) followed by nested polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. Methods PatientsArchived formalin-fixed, paraffin-embedded sections of liver biopsy specimens from 3 BCS patients with PV and 2 patients with hepatoportal sclerosis without PV were studied (Table 1). Hepatoportal sclerosis is a form of noncirrhotic portal hypertension and histologic portal venule abnormalities. 19 Access to the archived specimens was approved by the Institutional ...

Idiopathic myelofibrosis (IM) is likely the consequence of both the acquisition of genetic mutations and epigenetic changes that silence critical genes that control cell proliferation, differentiation, and apoptosis. We have explored the effects of the sequential treatment with the DNA methyltransferase inhibitor, decitabine [5-aza-2 ¶-deoxycytidine (5azaD)], followed by the histone deacetylase inhibitor, trichostatin A (TSA), on the behavior of IM CD34 + cells. Unlike normal CD34

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