JAK2V617F allele burden is associated with thrombotic mechanisms activation in polycythemia vera and essential thrombocythemia patients

• Published in: International journal of hematology Vol. 99; no. 1; pp. 32 - 40
• Main Authors: Coucelo, Margarida, Caetano, Gonçalo, Sevivas, Teresa, Almeida Santos, Susana, Fidalgo, Teresa, Bento, Celeste, Fortuna, Manuela, Duarte, Marta, Menezes, Cristina, Ribeiro, M. Letícia
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 2014; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Blood Platelets - metabolism; Case-Control Studies; CD11b Antigen - metabolism; Codon; Diseases of red blood cells; Female; Hematologic and hematopoietic diseases; Hematology; Hemorrhage - etiology; Humans; Janus Kinase 2 - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Monocytes - metabolism; Mutation; Neutrophils - metabolism; Oncology; Original Article; Platelet Activation; Platelet Aggregation; Polycythemia Vera - complications; Polycythemia Vera - genetics; Polycythemias; Quinacrine - metabolism; Thrombocythemia, Essential - complications; Thrombocythemia, Essential - genetics; Thromboplastin - metabolism; Thrombosis - etiology; Young Adult; Platelet activation; Leukocyte activation; JAK2V617F; Myeloproliferative neoplasms; Human; Hematology; Leukocyte; JAK2 protein tyrosine kinase; Cardiovascular disease; Polycythemia vera; Malignant hemopathy; Thrombosis; Mechanism; Vascular disease; Myeloproliferative syndrome; Essential thrombocythemia; Allele; Platelet function; Genetics; Cancer
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-013-1475-9

The clinical courses of polycythemia vera (PV) and essential thrombocythemia (ET) are characterized by thrombohemorrhagic diathesis. Several groups have suggested an association between JAK2V617F mutation and thrombosis. We hypothesized a relationship between JAK2V617F allele burden, cellular activation parameters, and thrombosis. We evaluated a group of PV and ET patients using flow cytometry: platelet CD62P, CD63, and dense granules, platelet–leukocyte aggregates (PLA), leukocyte CD11b and monocyte tissue factor (TF) expression. All patients had increased baseline platelet CD62P and CD63 expression ( p  < 0.05); 71 % of PV and 47 % of ET presented with a storage pool disease. Leukocyte CD11b, TF, and PLA were elevated in all patients. TF was higher in PV compared to ET ( p  < 0.05) and platelet–neutrophil [polymorphonuclear (PMN)] aggregates were increased in ET versus PV ( p  < 0.05). In ET, PLA were correlated with platelet numbers ( p  < 0.05). In all patients, JAK2V617F allele burden was directly correlated with monocyte CD11b. Patients with JAK2V617F allele burden >50 % presented higher levels of leukocyte activation. In ET, thrombosis was associated with JAK2V617F mutation ( p  < 0.05, χ 2  = 5.2), increased monocyte CD11b ( p  < 0.05) and with platelet-PMN aggregates ( p  < 0.05). In ET patients, hydroxyurea does not significantly reduce the activation parameters. Our data demonstrate that JAK2V617F allele burden is directly correlated with activation parameters that drive mechanisms that favor thrombosis.