Monocyte IL-2Ralpha expression is associated with thrombosis and the JAK2V617F mutation in myeloproliferative neoplasms

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2010-07, Vol.51 (1), p.67-72
• Main Authors: Goette, N P, Lev, P R, Heller, P G, Kornblihtt, L I, Korin, L, Molinas, F C, Marta, R F
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amino Acid Substitution - genetics; Case-Control Studies; Female; Humans; Interleukin-1beta - secretion; Interleukin-2 Receptor alpha Subunit - metabolism; Janus Kinase 2 - genetics; Male; Middle Aged; Monocytes - metabolism; Mutation - genetics; Myeloproliferative Disorders - complications; Myeloproliferative Disorders - enzymology; Myeloproliferative Disorders - pathology; Thrombocythemia, Essential - complications; Thrombocythemia, Essential - genetics; Thrombocythemia, Essential - pathology; Thrombosis - complications; Thrombosis - enzymology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Young Adult
• ISSN: 1096-0023
• DOI: 10.1016/j.cyto.2010.04.011

The development of bone marrow fibrosis and thrombosis are main causes of morbidity in essential thrombocythemia (ET). Monocyte activation has been associated to the production of fibrosis-related cytokines and pro-thrombotic factors. The aim of this study was to identify new markers of monocyte activation in Phi-negative myeloproliferative neoplasms and to search for their relationship with clinical features. Forty-five patients comprising 30 ET, eight myelofibrosis and seven polycythemia vera were included. We evaluated the alpha subunit of IL-2 receptor (CD25) on monocytes, basal and LPS-induced IL-1beta release from mononuclear cells, and monocyte TGF-beta mRNA content. Patients who had thrombotic events displayed higher monocyte CD25 levels (6.2%) than those without symptoms (1.3%) and controls (2.6%), p=0.0006. JAK2V617F-positive patients had higher monocyte CD25 expression levels (4.7%), than JAK2V617F-negative (2.6%), p=0.0213. Patients with myeloproliferative neoplasms had similar monocyte CD25 expression than controls, both, in basal conditions and after cell adhesion. IL-1beta release and TGF-beta mRNA levels were normal. In conclusion, increased monocyte CD25 expression is associated with history of thrombosis and is also up-regulated in patients harboring JAK2V617F mutation. The finding of increased CD25 levels together with normal IL-1beta and TGF-beta production reveals a selective monocyte activation profile in myeloproliferative neoplasms.