title: Monocyte IL-2Ralpha expression is associated with thrombosis and the JAK2V617F mutation in myeloproliferative neoplasms.
abstract: 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.
authors.affiliation: Sección Hematología Investigación, UE IDIM-CONICET, Instituto Alfredo Lanari, Universidad de Buenos Aires, Argentina. npgoette@gmail.com
authors.forename: N P
authors.initials: NP
authors.lastname: Goette
authors.forename: P R
authors.initials: PR
authors.lastname: Lev
authors.forename: P G
authors.initials: PG
authors.lastname: Heller
authors.forename: L I
authors.initials: LI
authors.lastname: Kornblihtt
authors.forename: L
authors.initials: L
authors.lastname: Korin
authors.forename: F C
authors.initials: FC
authors.lastname: Molinas
authors.forename: R F
authors.initials: RF
authors.lastname: Marta
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000150:complications* / Q000201:enzymology* / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000150:complications / Q000235:genetics / Q000473:pathology; D013927:Thrombosis / Q000150:complications* / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D053614:Janus Kinase 2