JAK2 V617F MUTATION AND PRV-1 OVEREXPRESSION: RELEVANCE IN THE DIAGNOSIS OF POLYCYTHAEMIA VERA AND ESSENTIAL THROMBOCYTHAEMIA

2009 ◽  
Vol 64 (5) ◽  
pp. 429-433
Author(s):  
S. Melis ◽  
S. Vellinga ◽  
P. Zachée ◽  
AC. Sierens ◽  
PJJC. De Schouwer
Keyword(s):  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
V617f Mutation

Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study

The Lancet ◽  
2005 ◽  
Vol 366 (9501) ◽  
pp. 1945-1953 ◽  
Author(s):  
Peter J Campbell ◽  
Linda M Scott ◽  
Georgina Buck ◽  
Keith Wheatley ◽  
Clare L East ◽  
...  
Keyword(s):  
Prospective Study ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Essential Thrombocythaemia ◽  
Mutation Status ◽  
V617f Mutation ◽  
Definition Of ◽  
A Prospective Study

scholarly journals A new case of dic(1;15) in essential thrombocythaemia with JAK2 V617F mutation

2012 ◽  
Author(s):  
Pereira Velloso ED Rodrigues ◽  
Ratis C Alonso ◽  
RK Kishimoto ◽  
Oliveira D Aquilino ◽  
Misael NC de Sousa ◽  
...  
Keyword(s):  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Essential Thrombocythaemia ◽  
V617f Mutation

The Red Cell Mass (RCM) Value In Polycythaemia Vera Disease In The JAK2 V617F Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5249-5249 ◽  
Author(s):  
Hassan A. Al-Jafar ◽  
Leena M Aytoglu ◽  
Issa Loutfi ◽  
Iman Al-Shemmari ◽  
Salem H Alshemmari
Keyword(s):  
Polycythemia Vera ◽  
Cell Mass ◽  
Jak2 V617f ◽  
Myeloproliferative Disorders ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Red Cell ◽  
Red Cell Mass ◽  
V617f Mutation ◽  
Idiopathic Erythrocytosis

Abstract Introduction In Polycythaemia Vera (PV), the RBC lineage is involved with increased haemoglobin, RBC count and haematocrit. WHO diagnostic criteria for PV are JAK2 V617F mutation and elevated red cell mass (RCM) > 25% of mean normal value. In addition, tests of marrow hypercellularity, blood erythropoietin and colony formation, are minor criteria. However, the diagnostic role of RCM test is still controversial and requires clarification. In this work, PV patients who had both an RCM study and JAK2 V617F mutation test, and routine laboratory tests, are evaluated to check if RCM was essential in the diagnostic work up for PV. Methods Over 2 years, 75 patients with abnormal haematocrit (men ≥ 0.50, women ≥ 0.45) had RCM and JAK2 V617F mutation tests (except JAK2 exon 12 mutation). All subjects consented to the study approved by the ethics committee. RCM was done by Cr-51 RBC radiolabeling method (no prior venesection at least 1 month). Statistical analysis involved descriptive statistics and chi-square test. Results There were 71 males and 4 females, mean age 46 y (range 17-75 y). Increased RCM was found in 41/75 (55%). Positive JAK2 V617F was found in 13/75 patients (17%), who also had RCM above the mean normal predicted value, however, when the WHO RCM criteria were applied, only 7/13 (54%) could be considered as having “truly” increased RCM. In the patient group with negative JAK2 V617F test, 12/28 (43%) had RCM results as per WHO criteria. There was no statistical association between presence of JAK2 V617F and the RCM values. Conclusion In patients with negative JAK2 V617F but with high clinical suspicion for PV and all other causes of secondary and idiopathic erythrocytosis excluded, an increase in RCM would support the diagnosis of PV (about 10 % PV cases). In patients with JAK2 positive mutation and high haematocrit but RCM below the WHO cut-off level, an increased RCM would still count to confirm the diagnosis as the current standard level seems too stringent. References James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature 2005; 434(7037): 1144-8. Kralovics R, Passamonti F, Buser AS, Soon-Siong T, Tiedt R, Passweg JR, et al. A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders. Merck Manual of Diagnosis and Therapy. 16th Edition, 1992 McMullin MF, Bareford D, Campbell P, Green AR, Claire Harrison C, Hunt B, Oscier D, et al. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. British Journal of Haematology 2005; 130(2): 174-95. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459-468. Pardanani A, Lasho TL, Finke C, et al. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007;21:1960-1963. Pancrazzi A, Guglielmelli P, Ponziani V, et al. A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction. J Mol Diagn. 2008;10:435-441. Disclosures: No relevant conflicts of interest to declare.

scholarly journals JAK2-V617F mutation in patients with myeloproliferative neoplasms: Association with FLT3-ITD mutation

2010 ◽  
Vol 138 (9-10) ◽  
pp. 614-618
Author(s):  
Vesna Spasovski ◽  
Natasa Tosic ◽  
Tatjana Kostic ◽  
Sonja Pavlovic ◽  
Milica Colovic
Keyword(s):  
Cell Proliferation ◽  
Myeloproliferative Neoplasms ◽  
Myeloid Cell ◽  
Jak2 V617f ◽  
Signalling Pathway ◽  
Janus Kinase ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Jak2 Mutation ◽  
V617f Mutation

Introduction. An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is the cause of uncontrolled proliferation in patients with myeloproliferative neoplasms. It is known that uncontrolled myeloid cell proliferation is also provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid leukaemia. Interestingly, mutated FLT3- ITD (internal tandem duplication) protein is a member of the same signalling pathway as JAK2 protein, the STAT5 signalling pathway. STAT5 activation is recognized as important for selfrenewal of haematopoetic stem cells. Objective. The aim of this study was the detection of JAK2- V617F mutation in patients with myeloproliferative neoplasms. Additionally, we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients in order to shed the light on the hypothesis of a similar role of these two molecular markers in haematological malignancies. Methods. Using allele-specific PCR, 61 patients with known or suspected diagnosis of myeloproliferative neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD mutation by PCR. Results. Eighteen of 61 analysed patients were positive for JAK2-V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera, and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was positive for FLT3-ITD mutation. Conclusion. This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell.

Congenital JAK2 V617F Polycythaemia Vera Cured with Sibling Allogeneic Bone Marrow Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5227-5227
Author(s):  
Kevin R Kelly ◽  
Corrina McMahon ◽  
Stephen Langabeer ◽  
Hassan Eliwan ◽  
Aengus O’Marcaigh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Mucosa ◽  
Blood Count ◽  
Allogeneic Bone Marrow Transplantation ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Full Blood Count ◽  
Polycythaemia Vera ◽  
Allogeneic Bone ◽  
V617f Mutation

Abstract Polycythaemia vera (PV) is extremely rare in young children. The Janus Kinase 2 V617F mutation is present in 95 % of adult PV patients. Testing is now widely available and has simplified the diagnostic workup. A previously healthy 7 month old girl was admitted to her local hospital with tonsillitis. Full blood count showed polycythaemia (Hb 19 g/dl) along with an elevated platelet (946 ×109/L) and white cell count (19.7 ×109/L). Oxygen saturations, arterial blood gases, chest x-ray, abdominal ultrasound and P50 were all normal. Serum erythropoietin was low. No mutations were identified in exons 7 and 8 of the EPO receptor gene, the Von Hipple Lindau tumour suppressor gene and the Prolyl hydroxylase domain 2 gene. Bone marrow aspirate and biopsy were showed hypercellularity, megakaryocyte hyperplasia and clustering along with erythroid hyperplasia. Cytogenetic analysis was normal. Spontaneous erythroid colonies were demonstrated. The JAK2 V617F mutation was found by polymerase chain reaction in her blood and in her Guthrie card taken at 2 days of age. Both parents and two of her siblings had normal full blood counts. Two further siblings have not had full blood counts. There is no known family history of myeloproliferative disorders. The JAK2 V617F mutation was not detected in the peripheral blood or the oral mucosa of either parent or in the oral mucosa of the patient. She was treated with regular venesection and aspirin 45mg OD was started when her platelet count rose above 1,500 × 109/L. Her clinical course and laboratory parameters remained stable with this treatment and no thromboembolic complications occurred. Due to the long term risks of malignant transformation and thromboembolism a sibling allogeneic bone marrow transplantation was performed with her 6 year old brother as a fully HLA matched, JAK2 V617F negative donor with a normal full blood count. A total nucleated count of 13 ×108 per kg recipient body weight, bone marrow was infused. The conditioning regimen was busulphan (4mg/kg/day × 5 days) and cyclophosphamide (50mg/kg/day × 4 days). Neutrophils rose to 2.6 ×109/L by day 24. No venous occlusive disease or graft versus host disease occurred. Complete donor chimerism and undetectable JAK2 V617F mutation have been observed from day + 14 to present. She remains in remission 15 months post transplant. She now has a normal full blood count and has not suffered any adverse sequelae. To the best of our knowledge this is the first report of prenatal JAK2 V617F PV. It further highlights the genotype-phenotype diversity that is seen amongst this group of JAK2 V617F positive myeloproliferative neoplasms. The frequency of the mutation in pediatric PV has been variably reported in the literature but this report proves that it can occur at all ages. The absence of the mutation in either parent or the oral mucosa of the child shows that this was likely an acquired somatic event that occurred in utero. The JAK2 V617F mutation is thought to be acquired in both familial and sporadic MPD. In a study of 22 families with PV the mutation was present in variable amounts in affected members and absent in unaffected members. Analysis of another single large family with PV showed the presence of JAK2 V617F in affected family members but not in an obligate carrier. This suggests that other genetic abnormalities, possibly inherited, precede the acquisition of the JAK2 V617F mutation. Inheritance of as yet unknown germline mutations may have predisposed towards the in utero acquisition of the somatic JAK2 V617F mutation in our particular case. Young children with PV face a considerable lifetime risk of arterial and venous thrombosis and of malignant transformation. Hemopoetic stem cell transplantation normalises the full blood count and eradicates the pre malignant clone thereby reducing these risks and should be considered early if a suitable donor is available.

scholarly journals Evaluation of High Resolution Melting Technique for Detection of JAK2-V617F Mutation in Formalin-Fixed Paraffin-Embedded Specimen from Myeloproliferative Neoplasm Cases

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Mohammad Reza Abdullahi ◽  
Nor Zamzila Abdullah ◽  
Rosmawati Ismail ◽  
Naznin Muhammad ◽  
Norlelawati A. Talib
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
V617f Mutation ◽  
Formalin Fixed

Myeloproliferative neoplasm (MPN) is a group of myeloid disorders which leads to erythrocytosis, thrombocytosis and leucocytosis. MPN with BCR-ABL positive is chronic myeloid leukaemia (CML) while BCR-ABL negative MPN includes polycythaemia Vera (PV), essential thrombocytemia (ET) and primary myelofibrosis (PMF). One of the major criteria for diagnosis of BCR-ABL negative MPN is the presence of JAK2-V617F mutation which is positive in 95% of PV and around 60% of ET and MF. Beside peripheral blood specimen, formalin-fixed paraffin-embedded (FFPE) marrow specimen can be used for detection of this mutation. Unfortunately, FFPE produces low quality DNA that put a challenge for successful amplification of DNA. We aimed to evaluate the utility of High Resolution Melting (HRM) analysis for detection of JAK2-V617F mutation in FFPE specimen from MPN cases. This study is a descriptive crosssectional study. Forty FFPE marrow specimens were retrieved from the years 2014-2016. Bio-Rad Precision Melt Analysis software was used for analysis of HRM data. Allele-specific PCR was done for validation of results. Positive samples were subjected to Sanger sequencing. JAK2-V617F mutation was positive in 13 out of 40 MPN cases. Level of agreement between HRM and AS-PCR was 97.5%. HRM is a rapid and powerful diagnostic assay which is suitable for detection of JAK2-V617F mutation in FFPE marrow specimen.

JAK2 V617F mutation is associated with increased risk of thrombosis in Chinese patients with essential thrombocythaemia

2008 ◽  
Vol 141 (6) ◽  
pp. 902-904 ◽  
Author(s):  
Raymond S. M. Wong ◽  
Chi-Keung Cheng ◽  
Natalie P. H. Chan ◽  
Suk-Hang Cheng ◽  
Wai-Shan Wong ◽  
...  
Keyword(s):  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Chinese Patients ◽  
Essential Thrombocythaemia ◽  
Increased Risk ◽  
V617f Mutation
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