Absence of mutations of the EPO‐receptor gene in Greek patients with familiar polycythemia

Bourantas, Lambros K.; Chatzikyriakidou, Anthoula; Dasoula, Aggeliki; Syrrou, Maria; Bourantas, Konstantinos L.; Georgiou, Ioannis

doi:10.1111/j.1600-0609.2006.00653.x

Cited by 7 publications

(7 citation statements)

References 7 publications

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“…These patients show, low serum EPO levels, normal haemoglobin oxygen affinities, and erythroid progenitors that exhibit EPO hypersensitivity [26]. Clinically, PFCP patients may present with symptoms ranging from headaches, dizziness, epistaxis, exertional dyspnea to pruritis after bathing [27]. Moreover, thrombotic and hemorrhagic events with premature morbidity and mortality have been reported [28], [29].…”

Section: Introductionmentioning

confidence: 99%

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

et al. 2010

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BackgroundGain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined.Methodology/Principal FindingsWe describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G→T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34+ cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway.Conclusions/SignificanceOur data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis.

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Section: Introductionmentioning

confidence: 99%

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

et al. 2010

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“…For example, in a study of 43 unrelated PFCP subjects, only five (12%) of the patients had EPOR mutations (Kralovics & Prchal, 2001). In another study, no mutation in the EpoR cytoplasmic domain was detected in PFCP patients from eight families of Greek origin (Bourantas et al, 2006). A caveat on the prevalence of EPOR mutations in PFCP was raised by Skoda and Prchal (2005).…”

Section: Other Unidentified Mutations In Pfcpmentioning

confidence: 99%

“…The natural history of PFCP shows no propensity to leukemic transformation nor is development of other myeloproliferative neoplasms observed (Prchal, 2005). Clinically, PFCP patients may present with symptoms ranging from headaches, dizziness, epistaxis, exertional dyspnea to pruritis after bathing (Bourantas et al , 2006). Thrombotic and hemorrhagic events with premature morbidity and mortality have been reported (Queisser et al , 1988; Prchal et al , 1995), but many appear to have a benign clinical course (Prchal et al , 1985; Juvonen et al , 1991; Emanuel et al , 1992).…”

Section: Erythrocytosismentioning

confidence: 99%

Advances in understanding the pathogenesis of primary familial and congenital polycythaemia

Huang¹,

Shen

Bulut³

2010

Br J Haematol

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SummaryPrimary familial and congenital polycythemia (PFCP) is an autosomal-dominant proliferative disorder characterized by erythrocytosis and hypersensitivity of erythroid progenitors to erythropoietin (Epo). Several lines of evidence suggest a causal role of truncated erythropoietin receptor (EpoR) in this disease. In this review, we discuss PFCP in the context of erythrocytosis and EpoR signalling. We focus on recent studies describing mechanisms underlying Epo-dependent EpoR down-regulation. One mechanism depends on internalization mediated through the p85 regulatory subunit of the Phosphoinositide 3-Kinase, and the other utilizes ubiquitin-based proteasomal degradation. Truncated PFCP EpoRs are not properly down-regulated upon stimulation, underscoring the importance of these mechanisms in the pathogenesis of PFCP.

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“…Short-term rhEPO induces HbF synthesis in vitro [33], in non-pregnant patients with thalassaemia or sickle cell disease [34][35][36][37][38][39] and in pregnant patients with thalassaemia [12]. Even high doses are well tolerated.…”

Section: Recombinant Human Hrythropoietinmentioning

confidence: 99%

Haemoglobinopathy in Pregnancy: Diagnosis and Treatment

Krafft¹,

Breymann

2004

CMC

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Haemoglobinopathies differ in geographic prevalence but together are amongst the most common genetic disorders worldwide. Despite huge diagnostic progress, therapeutic options remain limited, with many treatments still at the experimental stage, no more so than in pregnancy: not only does the presence of a fetus subject treatments to greater limitations, but also any worsening of the anaemia as pregnancy progresses results in higher fetomaternal morbidity and mortality. Anaemia weakens the response to peripartum blood loss, with the risk of postpartum complications. Until recently the standard conventional therapy for severe anaemia was (repeated) blood transfusion, with its well-known risks. Recombinant human erythropoietin (rhEPO) can induce fetal haemoglobin and is a safer, if less immediately effective, alternative for the correction of anaemia in pregnant patients with haemoglobinopathy.

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Absence of mutations of the EPO‐receptor gene in Greek patients with familiar polycythemia

Cited by 7 publications

References 7 publications

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

Advances in understanding the pathogenesis of primary familial and congenital polycythaemia

Haemoglobinopathy in Pregnancy: Diagnosis and Treatment

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