scholarly journals High HFE mutation incidence in idiopathic erythrocytosis

2018 ◽  
Vol 185 (4) ◽  
pp. 794-795 ◽  
Author(s):  
Bénédicte Burlet ◽  
Valentin Bourgeois ◽  
Céline Buriller ◽  
Bernard Aral ◽  
Fabrice Airaud ◽  
...  
Keyword(s):  
Hfe Mutation ◽  
Idiopathic Erythrocytosis

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

Idiopathic erythrocytosis: a study of a large cohort with a long follow-up

2015 ◽  
Vol 95 (2) ◽  
pp. 233-237 ◽  
Author(s):  
Maria Luigia Randi ◽  
Irene Bertozzi ◽  
Elisabetta Cosi ◽  
Claudia Santarossa ◽  
Edoardo Peroni ◽  
...  
Keyword(s):  
Large Cohort ◽  
Idiopathic Erythrocytosis

The course and complications of idiopathic erythrocytosis

2008 ◽  
Vol 1 (3) ◽  
pp. 189-196 ◽  
Author(s):  
T. C. PEARSON ◽  
G. WETHERLEY-MEIN
Keyword(s):  
Idiopathic Erythrocytosis

Idiopathic erythrocytosis: a disappearing entity

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 629-635 ◽  
Author(s):  
Mary Frances McMullin
Keyword(s):  
Progenitor Cell ◽  
Cell Mass ◽  
Young Patients ◽  
Erythropoietin Receptor ◽  
Erythroid Progenitor ◽  
Best Management ◽  
Number Of Patients ◽  
Clinical Consequences ◽  
The Common ◽  
Idiopathic Erythrocytosis

Abstract Erythrocytosis results when there is an increased red cell mass and thus an increased hemoglobin. The causes can be divided into primary intrinsic defects of the erythroid progenitor cell and secondary defects, where factors external to the erythroid compartment are responsible. Both can then be further divided into congenital and acquired categories. Congenital causes include mutations of the erythropoietin receptor and defects of the oxygen-sensing pathway including VHL, PHD2 and HIF2A mutations. When fully investigated there remain a number of patients in whom no cause can be elucidated who are currently described as having idiopathic erythrocytosis. Investigation should start with a full history and examination. Having eliminated the common entity polycythemia vera, further direction for investigation is guided by the erythropoietin level. Clinical consequences of the various erythrocytoses are not clear, but in some groups thromboembolic events have been described in young patients. Evidence is lacking to define best management, but aspirin and venesection to a target hematocrit should be considered.

The V617F JAK2 Mutation Is Very Uncommon in Idiopathic Erythrocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1295-1295
Author(s):  
Bruno Cassinat ◽  
Nathalie Parquet ◽  
Jean-Jacques Kiladjian ◽  
Gerald Massonnet ◽  
Marie-Laurence Menot ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Correct Diagnosis ◽  
Cell Mass ◽  
Red Cell ◽  
Normal Range ◽  
Jak2 Mutation ◽  
Taqman Probes ◽  
Red Cell Mass ◽  
The Impact ◽  
Idiopathic Erythrocytosis

Abstract The V617F JAK2 mutation is highly frequent in Polycythemia Vera (PV) patients. Indeed, we and others found the mutation in 70 to 90% of PV patients. However one of the most difficult differential diagnoses of PV is the idiopathic erythrocytosis (IE), as this diagnosis is based on negative criteria and exclusion of PV. However the differential diagnosis is of the utmost importance because IE is not considered as a clonal disease and should not transform to PV. Our centre is specialized in the diagnosis of myeloproliferative diseases, thus we have reviewed 22 cases with pure idiopathic erythrocytosis in the aim of defining the impact of V617F JAK2 mutation in this pathology. Median age of the patients was 46 (range: 29 to 67). Patients were diagnosed on the basis of an elevation of the hematocrit and a raised red cell mass without any identifiable cause of secondary erythrocytosis. PV diagnosis has been carefully excluded according to revised Pearson’s criteria. Median excess of red cell mass was +35% (range: +25% to +104%). Median hematocrit was 54% (range: 49% to 56%), median WBC (x109/L) was 6180 (range: 3500 – 8300) and median platelet count (x109/L) was 240 (range: 174 – 358). Serum Epo level was under or within the normal range in all patients except one case in whom an unexplained elevated level (x2 the upper normal limit) was found. Finally no splenomegaly was observed in these 22 patients. Because of the importance of a correct diagnosis distinguishing between PV and IE it was very important to test whether the JAK2 mutation could allow a correct classification. We have analysed DNA isolated from peripheral blood granulocytes. V617F JAK2 mutation was detected using a quantitative PCR and Taqman probes with a sensitivity of 2–4%. All of the 22 patients with IE were tested negative. This result confirms that IE is a distinct entity from PV, and also confirms the potential for the V617F JAK2 mutation detection to help in the differential diagnosis of erythrocytosis. Indeed, the presence of a JAK2 mutation in the context of erythrocytosis with increased red cell mass is highly specific of PV.

JAK2 Mutations at Exon 12 and 14 in Polycythemia Vera and Idiopathic Erythrocytosis: Incidence and Correlation with Clinical Characteristics.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2532-2532
Author(s):  
Carlos Besses ◽  
Luz Martínez-Avilés ◽  
Alberto Alvarez-Larrán ◽  
Francisco Cervantes ◽  
Juan Carlos Hernández-Boluda ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Cell Sorting ◽  
Clinical Characteristics ◽  
Clinical Phenotype ◽  
Cell Lineage ◽  
Jak2 V617f ◽  
Free Survival ◽  
Mutational Status ◽  
Cell Subpopulations ◽  
Idiopathic Erythrocytosis

Abstract Introduction. Exon 12 mutations of the JAK2 gene have been described in polycythemia vera (PV) and idiopathic erythrocytosis (IE) patients. These patients display a clinical phenotype different to that observed in V617F-positive PV patients, but no information is available on their clinical outcome. Patients and methods. Twenty JAK2 V617F-negative PV or IE patients and 86 V617F-positive PV patients were assessed for exon 12 and exon 14 mutations. Analysis of cell lineage mutational status was assessed following cell sorting. Aim. To analyze the presence of JAK2 mutations at exon 12 and 14 in a cohort of V617F-negative PV and IE patients and to correlate them with the patient clinicohematological and evolutive data. Results. Exon 12 mutations were detected in 4 (20%) V617F-negative patients (K539L, two cases, N542_E543del and H538_K539delinsL, one case each). In 16 patients, no mutations were found in either exon 12 or exon 14. Additional mutations in exon 14 were found in two V617F-positive patients. Two patients with exon 12 mutations developed thrombosis after diagnosis, with the probability of thrombosis-free survival being 75% at 5 years. Another patient with exon 12 mutation developed myelofibrosis at 20 years of PV diagnosis. JAK2 mutations were present in granulocytes, platelets and monocytes, but not in lymphocytes or NK cells. Conclusions. Patients harboring exon 12 mutations represent a subset of JAK2 V617F-negative PV or IE patients. These patients have initial hematological data different from V617F-positive patients, but they do not differ with regard to thrombosis development and myelofibrotic transformation. Table 1: JAK2 exon 12 and exon 14 mutations in blood cell subpopulations. Mutation Granulocytes Platelets CD14+ CD3+ CD19+ CD56+ * exon 12; # exon 14; + indicates the presence of the mutation; − indicates no detectable mutation ; ND not determined Patient 1* K539L (AAA →TTA) + + − − − − Patient 2* K539L (AAA →CTA) + + + − − − Patient 3* H538_K539delinsL + + ND − − ND Patient 4* N542_E543del + + + − − − Patient 5# V617F (GTC →TTT) + + − − − ND C618R (TGT →CGT) + + − − − ND Patient 6# V617F (GTC →TTC) + + + − − ND C616C (TGT →TGC) + + + − − ND

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.

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