scholarly journals Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Peijin Zhang ◽  
Yanyan Zhang ◽  
Jing Zhang ◽  
Hui Wang ◽  
He Ma ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Recessive Model ◽  
Elevated Risk ◽  
Budd Chiari Syndrome ◽  
Candidate Locus ◽  
Susceptibility Factor ◽  
Chiari Syndrome

Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR.Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P<0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04–90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07–69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31–15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings.

The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 3968-3973 ◽  
Author(s):  
Jasper H. Smalberg ◽  
Edith Koehler ◽  
Sarwa Darwish Murad ◽  
Aurelie Plessier ◽  
Susana Seijo ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Portal Vein ◽  
Clinical Presentation ◽  
Myeloproliferative Neoplasms ◽  
Nucleotide Polymorphism ◽  
Budd Chiari Syndrome ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Chiari Syndrome

Abstract The germline JAK2 46/1 haplotype has been associated with the development of JAK2V617F-positive as well as JAK2V617F-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2V617F-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2V617F-negative SVT patients did not differ from prevalence in the controls. However, JAK2V617F-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2V617F-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2V617F-positive SVT. In addition, our findings in JAK2V617F-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2V617F, that requires further exploration.

JAK2 Germline Genetic Variation In Budd-Chiari Syndrome and Portal Vein Thrombosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4212-4212
Author(s):  
Jasper Smalberg ◽  
Edith Koehler ◽  
Sarwa Darwish Murad ◽  
Aurelie Plessier ◽  
Juan-Carlos Garcia-Pagan ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Budd Chiari Syndrome ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Chiari Syndrome

Abstract Abstract 4212 Primary Budd-Chiari syndrome (BCS) and non-malignant, non-cirrhotic portal vein thrombosis (PVT) are rare disorders with a considerable overlap in etiology. Myeloproliferative neoplasms (MPN) are the most frequent underlying prothrombotic factor in both entities. The JAK2 V617F mutation (VF) has been identified in over half of the individuals with MPN. Recently, a JAK2 haplotype, designated ‘46/1’, has been described. Previous studies suggest that the JAK2 46/1 haplotype represents a disease susceptibility to MPN, independent of VF status. The aim of this study was to determine the role of the JAK2 46/1 haplotype in the etiology of BCS and PVT. Patients were recruited from the EN-Vie cohort, consisting of 163 BCS and 138 PVT patients, consecutively enrolled in nine European countries between October 2003 and October 2005. DNA was available from 116 BCS patients (50 males and 66 females; median age 38.1), 97 PVT patients (47 males and 50 females; median age 49.8) and 104 healthy controls (43 males and 61 females; median age 36.8). The JAK2 46/1 haplotype was tagged by the rs12343867 single nucleotide polymorphism. Frequency of the JAK2 haplotype 46/1 was higher in BCS (36%, p=0.06) compared to controls (27%), while similar in PVT patients (28%, p=0.89). When stratified for VF status, haplotype 46/1 frequency was higher in VF positive BCS (44%, p=0.01) and VF positive PVT patients (40%, p=0.06) compared to controls. Haplotype 46/1 frequency was similar in VF negative BCS (33%, p=0.29) and PVT patients (24%, p=0.47) compared to controls. VF negative BCS patients with a proven MPN also showed increased frequency of the 46/1 haplotype (56%, p=0.07). Logistic regression, adjusted for age and sex, showed an association between the 46/1 haplotype and risk of VF positive BCS (OR: 2.10; 1.16–3.80), VF positive PVT (OR 2.07; 0.95–4.52) and VF negative BCS patients with a proven MPN (OR 3.04; 1.02–9.06). We conclude that the JAK2 46/1 haplotype may be associated with BCS and that this was limited to patients with a proven MPN, independent of VF status. In PVT, the 46/1 haplotype was only associated with patients who were VF positive. This study was carried out on behalf of the European Network for Vascular Disorders of the Liver (EN-Vie). Disclosures: No relevant conflicts of interest to declare.

Polycythemia vera-geïnduceerd syndroom van Budd-Chiari bij een oudere patiënte

2021 ◽  
Author(s):  
S. VAN DESSEL ◽  
W. LALEMAN ◽  
E. GIELEN
Keyword(s):  
Polycythemia Vera ◽  
Myeloproliferative Neoplasms ◽  
Laboratory Data ◽  
Jak2 V617f ◽  
Budd Chiari Syndrome ◽  
Older Patient ◽  
Aged Patients ◽  
Chiari Syndrome ◽  
Hepatic Venous Outflow ◽  
Venous Outflow Obstruction

Polycythemia vera-induced Budd-Chiari syndrome in an older patient The case of a 94-year-old patient with subacute Budd-Chiari syndrome (BCS) caused by a novel diagnosis of polycythemia vera (PV) is reported. BCS is mostly seen in young or middle-aged patients. The presentation in a nonagenarian is rare, making this case exceptional. BCS is defined by a hepatic venous outflow obstruction. Its clinical presentation is variable from fulminant liver failure to an insidious form with symptoms of cirrhosis at the time of the diagnosis. In western countries, primary BCS is mainly seen, which is caused by an endoluminal lesion. A hypercoagulable state provoked by myeloproliferative neoplasms (MPN) is mostly responsible. The patient presented with abdominal distention and anorexia since two months. Physical examination revealed hepatomegaly and ascites. Laboratory data indicated polycythemia and cholestasis. The CT scan of the abdomen was diagnostic for subacute BCS. A JAK2-V617F mutation was found. The therapy consisted of anticoagulation, low-dose acetylsalicylic acid, phlebotomies and supportive care with diuretics and paracentesis.

Low burden of a JAK2-V617F mutated clone in monoclonal haematopoiesis in a Japanese woman with Budd-Chiari syndrome

2009 ◽  
Vol 89 (4) ◽  
pp. 517-522 ◽  
Author(s):  
Kohtaro Toyama ◽  
Masamitsu Karasawa ◽  
Arito Yamane ◽  
Hiromi Koiso ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Jak2 V617f ◽  
Japanese Woman ◽  
Budd Chiari Syndrome ◽  
Chiari Syndrome

Role of radiological imaging and interventions in management of Budd–Chiari syndrome

2018 ◽  
Vol 73 (7) ◽  
pp. 610-624 ◽  
Author(s):  
C.J. Das ◽  
M. Soneja ◽  
S. Tayal ◽  
A. Chahal ◽  
S. Srivastava ◽  
...  
Keyword(s):  
Radiological Imaging ◽  
Budd Chiari Syndrome ◽  
Chiari Syndrome

scholarly journals CALR mutations in a cohort of JAK2 V617F negative patients with suspected myeloproliferative neoplasms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tanja Belcic Mikic ◽  
Tadej Pajic ◽  
Matjaz Sever
Keyword(s):  
Sanger Sequencing ◽  
Blood Count ◽  
Mutation Detection ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Frameshift Mutations ◽  
Secondary Conditions ◽  
Non Invasive ◽  
Calr Mutations

AbstractSuspicion of myeloproliferative neoplasms (MPNs) and especially essential thrombocythemia (ET) in primary care is often based solely on blood counts, with patients referred to a haematologist without a thorough evaluation. We retrospectively assessed the role of calreticulin gene (CALR) mutations in the diagnosis of MPN in this population. We studied CALR mutations in 524 JAK2 V617F-negative patients with suspected MPN. Uncommon CALR mutations were confirmed by Sanger sequencing and searched for in the COSMIC or HGMD database. Mutations were defined as frameshift or non-frameshift mutations. CALR mutations were detected in 23 patients (23/524 = 4.4%). Four mutations detected in our study were newly identified mutations. Non-frameshift mutations were detected in two patients. Most patients (380/524 = 72.5%) were diagnosed with secondary conditions leading to blood count abnormalities such as iron deficiency, inflammatory and infectious diseases, malignancy and hyposplenism. Nine patients (9/23 = 39%) were retrospectively diagnosed with ET based on CALR mutation confirmation. Two patients with non-frameshift CALR mutations were diagnosed with reactive thrombocytosis and MPN unclassifiable, respectively. Our study showed that CALR mutations are important, non-invasive diagnostic indicators of ET and can aid in its diagnosis. Moreover, the type of CALR mutation must be accurately defined, as non-frameshift mutations may not be associated with ET. Finally, CALR mutation detection should be reserved for patients with high suspicion of clonal haematological disease.

scholarly journals Pattern of Vascular Involvement in Egyptian Patients with Budd-Chiari Syndrome: Relation to Etiology and Impact on Clinical Presentation

2018 ◽  
Vol 17 (4) ◽  
pp. 638-644 ◽  
Author(s):  
Mohammad A. Sakr ◽  
Sara M. Abdelhakam ◽  
Hany M. Dabbous ◽  
Ahmed S. Abdelmoaty ◽  
Hend E. Ebada ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Vascular Involvement ◽  
Budd Chiari Syndrome ◽  
Egyptian Patients ◽  
Chiari Syndrome

scholarly journals From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms

Blood ◽  
2019 ◽  
Vol 134 (22) ◽  
pp. 1902-1911 ◽  
Author(s):  
Brady L. Stein ◽  
Karlyn Martin
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Bleeding Complications ◽  
Budd Chiari Syndrome ◽  
Acquired Von Willebrand Syndrome ◽  
Chiari Syndrome ◽  
Appropriate Therapy ◽  
Von Willebrand

Stein and Martin provide a review of the thrombotic and bleeding complications of myeloproliferative neoplasms and provide a roadmap for appropriate therapy.

Direct Activation of STAT5 by TEL-Lyn Fusion Protein Promotes Induction of Myeloproliferative Neoplasms with Myelofibrosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4114-4114
Author(s):  
Yusuke Takeda ◽  
Chiaki Nakaseko ◽  
Hiroaki Tanaka ◽  
Masahiro Takeuchi ◽  
Makiko Yui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Signaling Molecules ◽  
Janus Kinase ◽  
Idiopathic Myelofibrosis ◽  
Lyn Kinase

Abstract Abstract 4114 Background Myeloproliferative neoplasms (MPN), a group of hematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. The V617F somatic mutation in the Janus kinase 2 (JAK2) gene has recently been found in the majority of patients with polycythemia vera (PV) and more than half of patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The expression of JAK2 V617F causes a PV-like disease with myelofibrosis in a murine bone marrow (BM) transplant model. In addition, a gain-of-function c-MPL W515 mutation was described in nearly 10% of patients with JAK2 V617F-negative IMF. However, the mechanism responsible for MPD and the formation of myelofibrosis in patients without JAK2 or c-MPL mutations is still unclear. We previously identified the fusion of the TEL gene to the Lyn gene (TEL-Lyn) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of TEL-Lyn into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged Lyn kinase in the pathogenesis of MPN with myelofibrosis. However, the signaling molecules directly downstream from and activated by TEL-Lyn remain unknown. Design and Methods We examined the signaling pathways activated by TEL-Lyn by Western blotting, immunoprecipitation, and in vitro kinase assay using a TEL-Lyn kinase-dead mutant as a control. We further characterized the functional properties of Stat5-deficient HSCs transduced with TEL-Lyn by colony-forming assay and bone marrow transplantation to evaluate the role of STAT5 in TEL-Lyn-induced MPN. Results TEL-Lyn was demonstrated to be constitutively active as a kinase through autophosphorylation. In TEL-Lyn-expressing cells, STAT5, STAT3, and Akt were constitutively activated. Among these signaling molecules, STAT5 was activated most prominently and this occurred without the activation of Jak2, the major kinase for STAT5. TEL-Lyn was co-immunoprecipitated with STAT5, and STAT5 was phosphorylated when incubated with TEL-Lyn, but not with TEL-Lyn kinase-dead mutant. These results indicate that TEL-Lyn interacts with STAT5 and directly activates STAT5 both in vitro and in vivo. Of note, the capacity of TEL-Lyn to support the formation of hematopoietic colonies under cytokine-free conditions in vitro and to induce MPN with myelofibrosis in vivo was profoundly attenuated in a Stat5-null background. Conclusions In this study, we clearly showed that TEL-Lyn directly activates STAT5 and the capacity of TEL-Lyn to induce MPN with myelofibrosis was profoundly attenuated in the absence of STAT5. Our findings of TEL-Lyn in this study support the role of the Src family kinases in the regulation of STAT pathways and implicate active Lyn in the alternative pathway for STAT activation in pathological cytokine signaling. Our mouse model of MPD with myelofibrosis would be beneficial for the analysis of therapeutic approaches for myelofibrosis. Disclosures: No relevant conflicts of interest to declare.

Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis

Blood ◽  
2012 ◽  
Vol 120 (25) ◽  
pp. 4921-4928 ◽  
Author(s):  
Jasper H. Smalberg ◽  
Lidia R. Arends ◽  
Dominique C. Valla ◽  
Jean-Jacques Kiladjian ◽  
Harry L. A. Janssen ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Myeloproliferative Neoplasms ◽  
Meta Analysis ◽  
Random Effects Model ◽  
Budd Chiari Syndrome ◽  
Vein Thrombosis ◽  
High Prevalence ◽  
Diagnostic Role ◽  
Chiari Syndrome

Abstract Myeloproliferative neoplasms (MPNs) are the most common cause of Budd-Chiari syndrome (BCS) and nonmalignant, noncirrhotic portal vein thrombosis (PVT). In this meta-analysis, we determined the prevalence of MPNs and their subtypes as well as JAK2V617F and its diagnostic role in these uncommon disorders. MEDLINE and EMBASE databases were searched. Prevalence of MPNs, JAK2V617F, and MPN subtypes were calculated using a random-effects model. A total of 1062 BCS and 855 PVT patients were included. In BCS, mean prevalence of MPNs and JAK2V617F was 40.9% (95% CI, 32.9%-49.5%) and 41.1% (95% CI, 32.3%-50.6%), respectively. In PVT, mean prevalence of MPNs and JAK2V617F was 31.5% (95% CI, 25.1%-38.8%) and 27.7% (95% CI, 20.8%-35.8%), respectively. JAK2V617F and MPNs were more frequent in BCS compared with PVT (P = .03 and P = .09, respectively). Polycythemia vera was more prevalent in BCS than in PVT (P = .001). JAK2V617F screening in splanchnic vein thrombosis (SVT) patients without typical hematologic MPN features identified MPN in 17.1% and 15.4% of screened BCS and PVT patients, respectively. These results demonstrate a high prevalence of MPNs and JAK2V617F in SVT patients and show differences in underlying etiology between these disorders. Furthermore, these results validate routine inclusion of JAK2V617F in the diagnostic workup of SVT patients.

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