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

Goette, Nora Paula; Lev, Paola Roxana; Heller, Paula G.; Kornblihtt, Laura; Korin, Laura; Molinas, Felisa C.; Marta, Rosana Fernanda

doi:10.1016/j.cyto.2010.04.011

Cited by 12 publications

(10 citation statements)

References 34 publications

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“…Both increased blood counts and cellular activation, which is due to hyperactivation of intracellular signaling pathways and enhanced interaction between blood cells, are implicated in the thrombotic predisposition. The key role of leukocytes in the pathogenesis of MPN thrombosis has been highlightened by several studies4567. Ongoing neutrophil activation, evidenced by increased membrane CD11b, release of proteolytic enzymes and neutrophil/platelet aggregates, contributes to the procoagulant phenotype56.…”

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confidence: 99%

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

Oyarzún

Carestia

Lev

et al. 2016

Sci Rep

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The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field.

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confidence: 99%

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

Oyarzún

Carestia

Lev

et al. 2016

Sci Rep

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“…Collectively, changes in biology with time or disease progression could be considered risk factors for PH. The monocyte count was higher in PMF patients with PH than that in those without PH; this is understandable because monocytes have been suggested to contribute to the vascular complications in MPNs [35,36]. However, it remains unclear why monocytes are involved only in PMF-associated PH, and not in PH associated with ET or PV.…”

Section: Discussionmentioning

confidence: 98%

Pulmonary hypertension in patients with Philadelphia-negative myeloproliferative neoplasms: a single-center retrospective analysis of 225 patients

et al. 2020

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Background The prevalence of pulmonary hypertension (PH) in myeloproliferative neoplasms (MPNs) varies among studies. We analyzed the prevalence of PH in Korean patients with Philadelphia-negative (Ph-) MPNs. Methods Medical records of patients with Ph-MPNs [essential thrombocythemia (ET), polycythemia vera (PV), or primary myelofibrosis (PMF)] visiting a single hospital between 1993 and 2019 were reviewed retrospectively. Transthoracic echocardiographic examination (TTE) results were reviewed and PH was diagnosed according to established guidelines.

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“…Studying leukocytes gained attention in MPN as it became apparent, they are not a mere by-product of the malignancy but also impact clinical outcomes. Leukocytosis is an independent risk factor for thrombosis ( 25 ) and there is growing evidence that activated monocytes contribute to MPN morbidity through secretion of pro-fibrotic cytokines and pro-thrombotic factors ( 26 ), regardless of their own mutational status ( 27 ). It has been shown that MPN patients with thrombotic events had higher levels of CD25 + monocytes compared to patients without thrombosis ( 26 ).…”

Section: Cellular Contributors To Inflammationmentioning

confidence: 99%

“…Leukocytosis is an independent risk factor for thrombosis ( 25 ) and there is growing evidence that activated monocytes contribute to MPN morbidity through secretion of pro-fibrotic cytokines and pro-thrombotic factors ( 26 ), regardless of their own mutational status ( 27 ). It has been shown that MPN patients with thrombotic events had higher levels of CD25 + monocytes compared to patients without thrombosis ( 26 ). MPN monocytes show an over-reactivity in their production of TNFA as a consequence of an impaired response to anti-inflammatory IL10, frequently elevated in MPN patients ( 27 ).…”

Section: Cellular Contributors To Inflammationmentioning

confidence: 99%

Remodeling the Bone Marrow Microenvironment – A Proposal for Targeting Pro-inflammatory Contributors in MPN

Jutzi

Mullally

2020

Front. Immunol.

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Philadelphia-negative myeloproliferative neoplasms (MPN) are malignant bone marrow (BM) disorders, typically arising from a single somatically mutated hematopoietic stem cell. The most commonly mutated genes, JAK2 , CALR , and MPL lead to constitutively active JAK-STAT signaling. Common clinical features include myeloproliferation, splenomegaly and constitutional symptoms. This review covers the contributions of cellular components of MPN pathology (e.g., monocytes, megakaryocytes, and mesenchymal stromal cells) as well as cytokines and soluble mediators to the development of myelofibrosis (MF) and highlights recent therapeutic advances. These findings outline the importance of malignant and non-malignant BM constituents to the pathogenesis and treatment of MF.

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

Cited by 12 publications

References 34 publications

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms

Pulmonary hypertension in patients with Philadelphia-negative myeloproliferative neoplasms: a single-center retrospective analysis of 225 patients

Remodeling the Bone Marrow Microenvironment – A Proposal for Targeting Pro-inflammatory Contributors in MPN

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