JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles

Hekimoğlu, Hilal; Toprak, Selin Fulya; Sözer, Selçuk

doi:10.4274/tjh.galenos.2021.2021.0607

Cited by 7 publications

(9 citation statements)

References 80 publications

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“…In multivariate analysis, venous thrombosis risk at any time was significantly higher in JAK2 V617F-mutated patients than that observed in CALR -mutated cases. This study confirmed the prothrombotic influence of JAK2 V617F [ 28 ] as opposed to CALR mutations [ 27 ]. In a study that included 168 ET patients, 51 (30.35%) experienced thrombotic events, 60% of which were arterial [ 29 ], and JAK2 V617F-mutated cases exhibited a 1.5-fold higher risk of developing thrombotic events.…”

Section: Discussionsupporting

confidence: 81%

Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients

Narlı Özdemir,

İpek,

Patir

et al. 2024

Tjh

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Objective: In this study, we investigated the effects of calreticulin ( CALR ) and JAK2 V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET). Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR - and JAK2 V617F-mutated ET patients were evaluated retrospectively. Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2 V617F- and CALR -positive, respectively. CALR -mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x10 9 /L vs. 709x10 9 /L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2 V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2 V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2 V617F- and CALR -mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2 V617F- and CALR -mutated patients. Thrombosis-free survival (TFS) was superior in CALR -mutated patients compared to JAK2 V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs. Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2 V617F and were associated with younger age at diagnosis. JAK2 V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

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Section: Discussionsupporting

confidence: 81%

Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients

Narlı Özdemir,

İpek,

Patir

et al. 2024

Tjh

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“…This finding could be a promising novel clue for predicting the progression of cerebral artery atherosclerosis in patients with MPNs. In the present study, the JAK2 V617F mutation was associated with JAK2 V617F-positive endothelial cells 15) . These previous experimental studies suggested the association of JAK2 V617F mutation with not only platelet aggregation but also arterial atherosclerosis.…”

Section: Discussionsupporting

confidence: 59%

“…In a previous study, the JAK2 V617F mutation caused inherent changes in platelet differentiation and reactivity with increased platelet aggregation in an ET mouse model 14) . The results of more recent studies suggest that the JAK2 V617F mutation affects platelets and other cell types, including neutrophils, macrophages, erythrocytes, and endothelial cells, leading to atherosclerosis [7][8][9]15) . Macrophages play important roles in the progression of atherosclerosis in Jak2 gene-modified mice by augmenting erythrophagocytosis, efferocytosis, DNA oxidative stress, and inflammation 7,8) .…”

Section: Discussionmentioning

confidence: 99%

<i>JAK2</i> V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms

Oyama,

Iwamoto,

Doyu

et al. 2023

JAT

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The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). Methods:We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. Results: A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. Conclusions:This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617Fmutated MPNs but also LCAD-related stroke.

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“…EGMs exhibit characteristics that are reflective of the cells from which they originate and provide profound information about the specific cell or tissue of origin [ 5 , 30 , 31 ]. The genetic and epigenetic profiles of EGMs such as distinct mutations on nucleic acids and specific methylation patterns, as well as immunophenotypic properties such as cell type-specific markers on EVs may provide further insight into the cell of origin, and allow a deeper understanding of the cellular characteristics and functions involved in disease mechanisms [ 10 , 32 ]. It is important to note that, EGMs have a broader role beyond intercellular communication.…”

Section: Extracellular Genomic Materials (Egms)mentioning

confidence: 99%

“…Depending on their specific genetic material, they can initiate various mechanisms in target cells. A recognizable example would be from tumor cells that might release EGMs with a mutation [ 10 ] or oncogenes [ 33 ]. When these EGMs target healthy cells, they can impact their physiology and trigger pathophysiological processes, potentially leading to the development of diseases [ 7 , 34 – 36 ].…”

Section: Extracellular Genomic Materials (Egms)mentioning

confidence: 99%

The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders

et al. 2023

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Extracellular Genomic Materials (EGMs) are the nucleic acids secreted or released from all types of cells by endogenous or exogenous stimuli through varying mechanisms into the extracellular region and inevitably to all biological fluids. EGMs could be found as free, protein-bound, and/ or with vesicles. EGMs can potentially have immunophenotypic and/or genotypic characteristics of a cell of origin, travel to distant organs, and interact with the new microenvironment. To achieve all, EGMs might bi-directionally transit through varying membranes, including the blood–brain barrier. Such ability provides the transfer of any information related to the pathophysiological changes in psychiatric disorders in the brain to the other distant organ systems or vice versa. In this article, many aspects of EGMs have been elegantly reviewed, including their potential in diagnosis as biomarkers, application in treatment modalities, and functional effects in the pathophysiology of psychiatric disorders. The psychiatric disorders were studied under subgroups of Schizophrenia spectrum disorders, bipolar disorder, depressive disorders, and an autism spectrum disorders. EGMs provide a robust and promising tool in clinics for prognosis and diagnosis. The successful application of EGMs into treatment modalities might further provide encouraging outcomes for researchers and clinicians in psychiatric disorders.

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JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles

Cited by 7 publications

References 80 publications

Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients

Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients

<i>JAK2</i> V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms

The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders

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