scholarly journals The Role of JAK2 in Myeloproliferative Diseases Diagnosis

2018 ◽  
Vol 1 (2) ◽  
pp. 135
Author(s):  
Yudith Annisa Ayu Rezkitha ◽  
S. Ugroseno Yudho Bintoro ◽  
Ami Ashariati
Keyword(s):  
Primary Myelofibrosis ◽  
Janus Kinase ◽  
Polycythaemia Vera ◽  
Janus Kinase 2 ◽  
Myeloproliferative Diseases ◽  
Diagnosis Criteria ◽  
Transduction Signal ◽  
Essential Thrombocytemia

Janus Kinase 2 (JAK2) plays an important role in mediating transduction signal of hematopoiesis, including in the pathogenesis of Myeloproliferative diseases (MPD). Various studies have been carried out to identify the position of aleles in tyrosine encoding mutations. Although the effect of JAK2 mutations is still not fully understood, the discovery of these mutations might be able to differentiate the types of polycythaemia vera, essential thrombocytemia, and primary myelofibrosis with malignant abnormalities. WHO has revised the MPD diagnosis criteria following this finding. This review will discuss the role of JAK2.

Role of the activating mutation Val617Phe of Janus kinase 2 gene in myeloproliferative diseases and significance of its detection

2007 ◽  
Vol 148 (5) ◽  
pp. 203-210 ◽  
Author(s):  
Hajnalka Andrikovics ◽  
Anikó Szilvási ◽  
Nóra Meggyesi ◽  
Viktória Király ◽  
Gabriella Halm ◽  
...  
Keyword(s):  
Unknown Origin ◽  
Janus Kinase ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Janus Kinase 2 ◽  
Idiopathic Myelofibrosis ◽  
Cell Counts ◽  
Myeloproliferative Syndrome ◽  
Activating Mutation

The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoetic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythaemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology. The goal of the present work was to establish simple molecular genetic techniques for the routine testing of Janus kinase 2 gene Val617Phe mutation, and to compare the clinical phenotypes of Val617Phe mutation positive and negative myeloproliferative syndromes. We employed the allele specific polymerase chain technique for detection of Val617Phe mutation in 252 patients with myeloproliferative syndrome. We measured Val617Phe frequency as 85,4% (117/137) in polycytaemia vera, 56,6% (56/99) in essential thrombocythaemia, and 87,5% (14/16) in idiopathic myelofibrosis. We found significantly elevated hemoglobin levels and white blood cell counts (measured at the time of diagnosis) in Val617Phe-positive polycythaemia vera and essential thrombocythaemia patient groups compared to Val617Phe-negative patients. However, the frequencies of splenomegaly and other complications (thrombosis, bleeding, transformation to acute leukemia) were not significantly different between the mutation-positive and negative groups. In conclusion, the non-invasive mutation analysis of the Janus kinase 2 Val617Phe is suitable for routine laboratory application and helps the differential diagnosis of myeloproliferative syndrome. Althought the exact role of Val617Phe mutation testing has not yet been identified on the basis of a broad professional consensus, the testing is suggested in cases of erythrocytoses and thrombocytoses of unknown origin.

scholarly journals Thrombosis in essential thrombocytemia and early/prefibrotic primary myelofibrosis: the role of the WHO histological diagnosis

2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Serena Rupoli ◽  
Gaia Goteri ◽  
Paola Picardi ◽  
Giorgia Micucci ◽  
Lucia Canafoglia ◽  
...  
Keyword(s):  
Primary Myelofibrosis ◽  
Histological Diagnosis ◽  
Essential Thrombocytemia

Atypical haematological presentation in a case of polycythaemia vera with a new variant mutation detected in exon 12: c.1605G>T (p.Met535Ile)

2017 ◽  
Vol 71 (2) ◽  
pp. 180-184 ◽  
Author(s):  
Amélia Soraia Andrade Pita ◽  
Ana Paula da Silva Azevedo ◽  
Alice Reichert ◽  
Cândido José Pimenta da Silva ◽  
Vanessa Henriques ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Novel Mutation ◽  
Janus Kinase ◽  
Polycythaemia Vera ◽  
Janus Kinase 2 ◽  
Gain Of Function ◽  
New Variant

One of the major genetic insights into the pathogenesis of polycythaemia vera included the identification of the somatic point gain-of-function mutations in Janus kinase 2 gene—first JAK2V617F on exon 14, present in 95%–97% of the cases, and later on exon 12. In the literature, we can find some reported studies where different exon 12 mutations are identified. Unlike patients with JAK2V617F mutation in exon 14, the mutation at exon 12 is not usually associated with an increase in the three haematopoietic series (erythrocytosis, leucocytosis and thrombocytosis). It appears to be associated with a distinct syndrome, mostly characterised by isolated and more marked erythrocytosis, independently of the mutational variant. We report here the case of a patient who is JAK2exon 12 positive, presenting a novel mutation—c.1605G>T (p.Met535Ile)—associated with c.1612C>T (p.His538Tyr) mutation previously described, evidencing an atypical clinical phenotype.

scholarly journals Platelet Dysfunction and Thrombosis in JAK2 V617F -Mutated Primary Myelofibrotic Mice

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Shinobu Matsuura ◽  
Cristal R. Thompson ◽  
Mostafa Elmokhtra Belghasem ◽  
Roelof H. Bekendam ◽  
Andrew Piasecki ◽  
...  
Keyword(s):  
Mouse Model ◽  
Platelet Activation ◽  
Vascular Injury ◽  
Thrombus Formation ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Dense Granule ◽  
Janus Kinase ◽  
Moderate Increase ◽  
Janus Kinase 2

Objective: The risk of thrombosis in myeloproliferative neoplasms, such as primary myelofibrosis varies depending on the type of key driving mutation (JAK2 [janus kinase 2], CALR [calreticulin], and MPL [myeloproliferative leukemia protein or thrombopoietin receptor]) and the accompanying mutations in other genes. In the current study, we sought to examine the propensity for thrombosis, as well as platelet activation properties in a mouse model of primary myelofibrosis induced by JAK2 V617F (janus kinase 2 with valine to phenylalanine substitution on codon 617) mutation. Approach and Results: Vav1-hJAK2 V617F transgenic mice show hallmarks of primary myelofibrosis, including significant megakaryocytosis and bone marrow fibrosis, with a moderate increase in red blood cells and platelet number. This mouse model was used to study responses to 2 models of vascular injury and to investigate platelet properties. Platelets derived from the mutated mice have reduced aggregation in response to collagen, reduced thrombus formation and thrombus size, as demonstrated using laser-induced or FeCl 3 -induced vascular injury models, and increased bleeding time. Strikingly, the mutated platelets had a significantly reduced number of dense granules, which could explain impaired ADP secretion upon platelet activation, and a diminished second wave of activation. Conclusions: Together, our study highlights for the first time the influence of a hyperactive JAK2 on platelet activation-induced ADP secretion and dense granule homeostasis, with consequent effects on platelet activation properties.

Role of a Janus kinase 2-dependent signaling pathway in platelet activation

2014 ◽  
Vol 133 (6) ◽  
pp. 1088-1096 ◽  
Author(s):  
Wan-Jung Lu ◽  
Kao-Chang Lin ◽  
Shih-Yi Huang ◽  
Philip Aloysius Thomas ◽  
Yu-Hua Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Platelet Activation ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Dependent Signaling Pathway

The role of Janus kinase 2 (JAK2) activation in pneumococcal EstA protein-induced inflammatory response in RAW 264.7 macrophages

2011 ◽  
Vol 51 (4) ◽  
pp. 297-303 ◽  
Author(s):  
Elias Gebru ◽  
Eun-Hee Kang ◽  
Dereje Damte ◽  
Joong-Su Lee ◽  
Seung-Hee Jang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Janus Kinase ◽  
Raw 264.7 ◽  
Janus Kinase 2 ◽  
Raw 264.7 Macrophages

Improved Survival of Calreticulin-Mutated Patients Compared With Janus Kinase 2 in Primary Myelofibrosis: A Meta-Analysis

2016 ◽  
Vol 16 (5) ◽  
pp. 264-268 ◽  
Author(s):  
Hampig Raphael Kourie ◽  
Lieveke Ameye ◽  
Marianne Paesmans ◽  
Dominique Bron
Keyword(s):  
Meta Analysis ◽  
Primary Myelofibrosis ◽  
Janus Kinase ◽  
Janus Kinase 2

scholarly journals Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1394 ◽  
Author(s):  
Mi-Ae Kang ◽  
Jongsung Lee ◽  
Sang Ha ◽  
Chang Lee ◽  
Kyoung Kim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proliferation Rate ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Forkhead Box ◽  
Cell Proliferation Rate

Specific kinds of interleukin (IL) receptors are known to mediate lymphocyte proliferation and survival. However, recent reports have suggested that the high expression of IL4Rα and IL13Rα1 in tumor tissue might be associated with tumorigenesis in several kinds of tumor. We found that a significant association between mRNA level of IL4Rα or IL13Rα1 and the poor prognosis of renal cell carcinoma (RCC) from the public database (http://www.oncolnc.org/). Then, we evaluated the clinicopathological significance of the immunohistochemical expression of IL4Rα and IL13Rα1 in 199 clear cell RCC (CCRCC) patients. The individual and co-expression patterns of IL4Rα and IL13Rα1 were significantly associated with cancer-specific survival (CSS) and relapse-free survival (RFS) in univariate analysis. Multivariate analysis indicated IL4Rα-positivity and co-expression of IL4Rα and IL13Rα1 as the independent indicators of shorter CSS and RFS of CCRCC patients. For the in vitro evaluation of the oncogenic role of IL4Rα and IL13Rα1 in RCC, we knock-downed IL4Rα or IL13Rα1 and observed that the cell proliferation rate was decreased, and the apoptosis rate was increased in A498 and ACHN cells. Furthermore, we examined the possible role of Janus kinase 2 (JAK2), well-known down-stream tyrosine kinase under the heterodimeric receptor complex of IL4Rα and IL13Rα1. Interestingly, JAK2 interacted with Forkhead box O3 (FOXO3) to cause tyrosine-phosphorylation of FOXO3. Silencing IL4Rα or JAK2 in A498 and ACHN cells reduced the interaction between JAK2 and FOXO3. Moreover, pharmacological inhibition of JAK2 induced the nuclear localization of FOXO3, leading to increase apoptosis and decrease cell proliferation rate in A498 and ACHN cells. Taken together, these results suggest that IL4Rα and IL13Rα1 might be involved in the progression of RCC through JAK2/FOXO3 pathway, and their expression might be used as the novel prognostic factor and therapeutic target for RCC patients.

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