Melanie J Percy

..Continued study of idiopathic cases of erythrocytosis with raised serum Epo will reveal whether HIF-2 alpha will be a major cause of erythrocytosis on par with VHL...

..Our findings indicate that PHD2 is critical for normal regulation of HIF in humans...

..These findings support the importance of HIF-2 alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis...

..The aims of this study were to assess the prevalence of JAK2 exon 12 mutations in IE patients, and to determine the associated clinicopathological features...

..These findings substantiate PHD2 as a critical enzyme controlling HIF and therefore Epo in humans, and furthermore suggest the location of an active site groove in PHD2 that binds HIF...

..The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE)...

..We concluded that the BCSH criteria were the most accurate diagnostic criteria for PV as they had an acceptable level of sensitivity and could differentiate between PV and other erythrocytoses...

..This single mutation is widespread having been detected in related MPD and other haematological malignancies. This leads to a number of further questions about the role of this single mutation in the clinical pattern of disease...

..Our functional studies indicate that this mutation leads to stabilization of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults...

..Identification of the disease-causing genes will enable better classification of familial and acquired erythrocytosis and thrombocytosis. Furthermore, it will provide an insight into the mechanisms regulating myeloid cell proliferation...

..Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc...

..The infant was started on daily ascorbic acid treatment. She has very mild cyanosis and normal growth and developmental parameters on follow-up at 10 months of age...

..Thirty-three different mutations have now been recorded for RCM. The original authors' optimism that RCM would provide material for future genetic studies has been amply justified...

..Specific mutations in the CYB5R gene are not exclusive to each type...

..The development of a heterologous expression system has allowed the impact of naturally occurring variants of cb(5)r to be assessed and has provided insight into the function of cb(5)r...

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..Disorders of oxidised haemoglobin are relatively easily diagnosed and in most cases, except for the presence of congenitally defective haemoglobin M, can be treated successfully...

..This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL-HIF pathway in systemic human cardiopulmonary physiology...

..A recent report of familial erythrocytosis now implicates a different protein, Prolyl Hydroxylase Domain protein 2 (PHD2), which is an enzyme that hydroxylates HIF...

..It remains to be established what role this mutation, which gives cells a proliferative advantage, might play in the pathogenesis and prognosis of rare atypical MPD...

..One patient (1.6%) was found to have this mutation, and has remained stable for 9 years, suggesting that the JAK2 V617F mutation is rare in patients with idiopathic erythrocytosis...

..Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio=8.20, P=0.0057)...

..Haplotype analysis indicated a founder effect. We conclude that the VHL 598C>T mutation, the most common defect of congenital polycythemia yet found, was spread from a single founder 1,000 to 62,000 years ago...

..Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity...