当前位置： SCI文献检索 > BRITISH JOURNAL OF HAEMATOLOGY期刊下所有文献 > Polycythaemia-inducing mutations in the erythropoietin receptor (EPOR): mechanism and function as elucidated by epidermal growth factor receptor-EPOR chimeras.

Polycythaemia-inducing mutations in the erythropoietin receptor (EPOR): mechanism and function as elucidated by epidermal growth factor receptor-EPOR chimeras.

Abstract：

:Primary familial and congenital polycythaemia (PFCP) is a disease characterized by increased red blood cell mass, and can be associated with mutations in the intracellular region of the erythropoietin (EPO) receptor (EPOR). Here we explore the mechanisms by which EPOR mutations induce PFCP, using an experimental system based on chimeric receptors between epidermal growth factor receptor (EGFR) and EPOR. The design of the chimeras enabled EPOR signalling to be triggered by EGF binding. Using this system we analysed three novel EPOR mutations discovered in PFCP patients: a deletion mutation (Del1377-1411), a nonsense mutation (C1370A) and a missense mutation (G1445A). Three different chimeras, bearing these mutations in the cytosolic, EPOR region were generated; Hence, the differences in the chimera-related effects are specifically attributed to the mutations. The results show that the different mutations affect various aspects related to the signalling and metabolism of the chimeric receptors. These include slower degradation rate, higher levels of glycan-mature chimeric receptors, increased sensitivity to low levels of EGF (replacing EPO in this system) and extended signalling cascades. This study provides a novel experimental system to study polycythaemia-inducing mutations in the EPOR, and sheds new light on underlying mechanisms of EPOR over-activation in PFCP patients.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Gross M,Ben-Califa N,McMullin MF,Percy MJ,Bento C,Cario H,Minkov M,Neumann D

doi

10.1111/bjh.12782

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

519-28

issue

4

eissn

0007-1048

issn

1365-2141

journal_volume

165

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF HAEMATOLOGY文献大全
  • Rapid proteolysis of unstable globins in human bone marrow.

    abstract：:To determine whether human red cells contain a proteolytic system capable of rapidly degrading unstable proteins, the fate of pulse-labelled puromycyl polypeptides was investigated. In erythroid bone marrow cells these unstable polypeptides were degraded to TCA-soluble fragments with a mean half-life of 4 . 5 min. How...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1983.tb02042.x

    authors： Vissers MC,Winterbourn CC,Carrell RW

    更新日期：1983-03-01 00:00:00

  • Cellular and humoral immune responses in haemophiliacs after vaccination against tick-borne encephalitis.

    abstract：:The primary immune response to a viral antigen (tick-borne encephalitis, TBE) has been determined in haemophiliacs. Twelve HIV-negative and four clinically asymptomatic, HIV-positive haemophiliacs as well as 16 age-matched healthy controls were included in the study. Antibody responses after TBE vaccination were compa...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1992.tb06432.x

    authors： Wolf HM,Pum M,Jáger R,István L,Mannhalter JW,Eibl MM

    更新日期：1992-10-01 00:00:00

  • Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura.

    abstract：:The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 IT...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2002.03612.x

    authors： Kohda K,Kuga T,Kogawa K,Kanisawa Y,Koike K,Kuroiwa G,Hirayama Y,Sato Y,Niitsu Y

    更新日期：2002-08-01 00:00:00

  • Large granular lymphocytic leukaemia after solid organ and haematopoietic stem cell transplantation.

    abstract：:T-cell large granular lymphocytic leukaemia (T-LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T-LGLL seen at our institution over the last 10 years, we encountered 15 cas...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.16336

    authors： Awada H,Mahfouz RZ,Durrani J,Kishtagari A,Jagadeesh D,Lichtin AE,Hill BT,Hamilton BK,Carraway HE,Nazha A,Majhail NS,Sobecks R,Visconte V,Kalaycio M,Sekeres MA,Maciejewski JP

    更新日期：2020-04-01 00:00:00

  • N-RAS mutations in T-cell acute lymphocytic leukaemia: analysis by direct sequencing detects a novel mutation.

    abstract：:A novel mutation of the N-RAS gene of T-ALL blast cells was detected by a direct sequencing of in vitro amplified exon-1 of the N-RAS gene. Threonine (ACA) was substituted for alanine (GCA) at codon 11. This mutation would have been overlooked by conventional probe hybridization techniques. A search for other mutation...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1989.tb07648.x

    authors： Bar-Eli M,Ahuja H,Foti A,Cline MJ

    更新日期：1989-05-01 00:00:00

  • The exchangeable splenic platelet pool in response to selective adrenergic beta-i-receptor blockade.

    abstract：:The aim of the present work was to investigate the effect of selective beta-I-blockade on the exchangeable splenic platelet pool (ESPP). Therefore, 50 mg of metoprolol (a selective beta-I-receptor blocking agent) was given by mouth to three groups of subjects: (1) 15 healthy volunteers, (2) five asplenic subjects, and...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1977.tb06844.x

    authors： Kutti J,Fredén K,Melberg PE,Lundborg P

    更新日期：1977-10-01 00:00:00

  • The promise of chimeric antigen receptor T cells (CARTs) in leukaemia.

    abstract：:The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, bu...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.14475

    authors： Orlowski RJ,Porter DL,Frey NV

    更新日期：2017-04-01 00:00:00

  • Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects.

    abstract：:Among 80 hereditary spherocytosis (HS) kindreds studied using denaturing electrophoretic separation of solubilized eythrocyte membrane proteins, we recognized three prominent subsets: HS with isolated spectrin deficiency, HS with combined spectrin and ankyrin deficiency, and HS with band 3 deficiency These three subse...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1997.1893005.x

    authors： Dhermy D,Galand C,Bournier O,Boulanger L,Cynober T,Schismanoff PO,Bursaux E,Tchernia G,Boivin P,Garbarz M

    更新日期：1997-07-01 00:00:00

  • Long-standing remission after 25-OH D3 treatment in a case of chronic myelomonocytic leukaemia.

    abstract：:This report describes a case of chronic myelomonocytic leukaemia (CMML) in whom a complete remission was achieved and sustained 15 months after treatment with 25-OH vitamin D3. No side-effects were observed. Although vitamin D1 has been used in the treatment of myelodysplastic syndromes, to our knowledge this is the f...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1993.tb03230.x

    authors： Mellibovsky L,Díez A,Aubia J,Nogues X,Pérez-Vila E,Serrano S,Recker RR

    更新日期：1993-12-01 00:00:00

  • Less than half of patients aged 65 years or under with myeloma proceed to transplantation: results of a two region population-based survey.

    abstract：:In this population-based survey covering two geographically distinct UK regions, we evaluated the number of myeloma patients aged < or =65 years who have not undergone transplantation. The combined data from both of these regions showed that 57% of age-eligible patients were not transplanted. While early death and com...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2004.05340.x

    authors： Morris TC,Velangi M,Jackson G,Marks DI,Ranaghan L,Northern Ireland Regional Haematology Group.,Northern Regional Haematologists Group.,Clinical Trials Committee of The British Scoiety for Blood and Marrow Transplantation.

    更新日期：2005-02-01 00:00:00

  • Specific binding between human neutrophils and heparin.

    abstract：:Heparin binding on polymorphonuclear leucocytes (PMNL) was characterized. Heparin binding was specific, rapid, saturable and reversible. One single class of heparin binding sites was found with a dissociation constant of 1.22 mumol/l and 7.7 x 10(6) sites per PMNL. The binding was independent of the anticoagulant acti...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1992.tb08176.x

    authors： Leculier C,Benzerara O,Couprie N,Francina A,Lasne Y,Archimbaud E,Fiere D

    更新日期：1992-05-01 00:00:00

  • Filgrastim-induced stem cell mobilization in chronic myeloid leukaemia patients during imatinib therapy: safety, feasibility and evidence for an efficient in vivo purging.

    abstract：:Therapy with imatinib mesylate is limited by cellular resistance in chronic myeloid leukaemia (CML). Further, the limited availability of matching stem cell donors or an unfavourable risk profile for allogeneic stem cell transplantation (SCT) reduces the number of therapeutic options in a number of patients. To assess...

    journal_title：British journal of haematology

    pub_type： 临床试验,杂志文章

    doi：10.1046/j.1365-2141.2003.04756.x

    authors： Kreuzer KA,Klühs C,Baskaynak G,Movassaghi K,Dörken B,le Coutre P

    更新日期：2004-01-01 00:00:00

  • Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database.

    abstract：:This study assessed the incidence of immune thrombocytopenia (ITP) and characteristics associated with ITP in the paediatric population using the General Practice Research Database (GPRD). Two hundred and fifty-seven paediatric ITP patients were identified out of 1145 incident patients with ITP recorded between 1990 a...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2010.08176.x

    authors： Yong M,Schoonen WM,Li L,Kanas G,Coalson J,Mowat F,Fryzek J,Kaye JA

    更新日期：2010-06-01 00:00:00

  • Expression of several members of the TNF-ligand and receptor family on tonsillar lymphoid B cells.

    abstract：:Although the expression patterns of the members of the tumour necrosis factor receptor and ligand families have extensively been studied by flow-cytometry on stimulated peripheral blood mononuclear cells (PBMNC), little or no flow-cytometric or immunohistological data exist about their expression in lymphoid tissue. A...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1997.3153134.x

    authors： Dürkop H,Anagnostopoulos I,Bulfone-Paus S,Stein H

    更新日期：1997-09-01 00:00:00

  • Differentiation of patients with subtype IIb-like von Willebrand's disease by means of perfusion experiments with reconstituted blood.

    abstract：:Four unrelated patients with a bleeding diathesis (bleeding time longer than 30 min), some spontaneous platelet aggregation, thrombocytopenia and large platelets, had decreased levels of factor VIII-von Willebrand factor (FVIII-VWF) related properties and impaired platelet adherence to human artery subendothelium. The...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1985.tb07333.x

    authors： Sakariassen KS,Nieuwenhuis HK,Sixma JJ

    更新日期：1985-03-01 00:00:00

  • The C807T/G873A polymorphism in the platelet glycoprotein Ia gene and the risk of acute coronary syndrome in the Italian population.

    abstract：:Membrane glycoprotein (GP) Ia/IIa mediates platelet adhesion to collagen. The linked C807T/G873A polymorphisms in the GP Ia gene are correlated with a variable expression of the platelet surface receptor, the 807 TT/873 AA genotype being associated with a higher receptor density. Our study aimed to evaluate the possib...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2001.02868.x

    authors： Casorelli I,De Stefano V,Leone AM,Chiusolo P,Burzotta F,Paciaroni K,Rossi E,Andreotti F,Leone G,Maseri A

    更新日期：2001-07-01 00:00:00

  • Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults.

    abstract：:Sources for allogeneic stem cells for patients with haematological disorders lacking a histocompatible sibling donor include matched unrelated donor (MUD) and umbilical cord blood (UCB). A total of 51 patients with haematological disorders, treated with myeloablation and transplantation with either unrelated human leu...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2003.04792.x

    authors： Hamza NS,Lisgaris M,Yadavalli G,Nadeau L,Fox R,Fu P,Lazarus HM,Koc ON,Salata RA,Laughlin MJ

    更新日期：2004-02-01 00:00:00

  • Immunoreactive prolyl hydroxylase in patients with primary and secondary myelofibrosis.

    abstract：:Prolyl hydroxylase (PH) is an important enzyme in collagen synthesis. It is required for the hydroxylation of prolyl residues in peptide chains in collagen synthesis. Serum PH activity was measured in patients with primary myelofibrosis (agnogenic myeloid metaplasia and myelofibrosis with prior history of polycythaemi...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1987.tb02260.x

    authors： Wang JC,Wong C,Kao WW

    更新日期：1987-02-01 00:00:00

  • Essential role for T cells in human B-cell lymphoproliferative disease development in severe combined immunodeficient mice.

    abstract：:Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease (BLPD)-like lesions develop in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors. We used this model to investigate the pathogenesis of EBV-associated BLPD. Tumour inci...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2000.02066.x

    authors： Johannessen I,Asghar M,Crawford DH

    更新日期：2000-06-01 00:00:00

  • High-dose therapy improves the bone remodelling compartment canopy coverage and bone formation in multiple myeloma.

    abstract：:Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling. Loss of this canopy ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.13584

    authors： Hinge M,Delaisse JM,Plesner T,Clasen-Linde E,Salomo M,Andersen TL

    更新日期：2015-11-01 00:00:00

  • Chronic lymphocytic leukaemia--the role of the microenvironment pathogenesis and therapy.

    abstract：:Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL) is one of the more common forms of B cell malignancy. Although the condition has a variable clinical course, the trend is towards eventual relapse and the disease is considered incurable. Whilst the majority of the circulating CD5-positive neoplastic B cel...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.12344

    authors： Ramsay AD,Rodriguez-Justo M

    更新日期：2013-07-01 00:00:00

  • Cocoa: a new mouse model for platelet storage pool deficiency.

    abstract：:We describe genetic, haematological and biochemical properties of a new mouse pigment mutant, cocoa (coa). Cocoa is a recessive mutation located on the centromeric end of chromosome 3 near the Car-2 locus. The mutation causes increased bleeding time accompanied by symptoms of platelet storage pool deficiency (SPD), in...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1988.tb02376.x

    authors： Novak EK,Sweet HO,Prochazka M,Parentis M,Soble R,Reddington M,Cairo A,Swank RT

    更新日期：1988-07-01 00:00:00

  • Intercellular communication between bone marrow stromal cells and CD34+ haematopoietic progenitor cells is mediated by connexin 43-type gap junctions.

    abstract：:The existence of functional gap junctions between haematopoietic progenitor cells (HPCs) and stromal cells of the haematopoietic microenvironment in the human system is a controversial issue. Primary CD34+ HPCs isolated from leukapheresis products were co-incubated with the human fibroblastoid bone marrow stromal cell...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2000.02385.x

    authors： Dürig J,Rosenthal C,Halfmeyer K,Wiemann M,Novotny J,Bingmann D,Dührsen U,Schirrmacher K

    更新日期：2000-11-01 00:00:00

  • Advances in the understanding of myeloma bone disease and tumour growth.

    abstract：:Advances in multiple myeloma support the notion that the associated bone disease, characterized by increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and necessity of tumour progression. Osteoblastogenesis is suppressed by secreted inhibitors and dysregulation of cell-surface 'coupli...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/j.1365-2141.2010.08141.x

    authors： Yaccoby S

    更新日期：2010-05-01 00:00:00

  • Erythropoiesis and mean red-cell lifespan in normal subjects and in patients with the anaemia of active rheumatoid arthritis.

    abstract：:Recently developed ferrokinetic methods offer a tool to measure effective and ineffective erythropoiesis and mean red-cell lifespan (Ricketts et al, 1975). We have used this tool to investigate erythropoiesis in normal subjects and in patients with the anaemia of active rheumatoid arthritis. In normal subjects the res...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1978.tb01114.x

    authors： Dinant HJ,de Maat CE

    更新日期：1978-07-01 00:00:00

  • Severe congenital neutropenia unresponsive to G-CSF.

    abstract：:Severe congenital neutropenia (SCN) is an inherited disorder characterized by severe neutropenia and recurrent infections from an early age, with bone marrow showing a maturational arrest of granulopoiesis at the promyelocyte stage. Since the introduction of G-CSF therapy the prognosis for affected children has improv...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1995.tb05242.x

    authors： Ryan M,Will AM,Testa N,Hayworth C,Darbyshire PJ

    更新日期：1995-09-01 00:00:00

  • Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction.

    abstract：:Pathogen reduction (PR) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness. We conducted a multicentre, open-label, randomized, non-inferiority trial comparing the clinical effectiveness of buffy-coat derived leukoreduced platelet co...

    journal_title：British journal of haematology

    pub_type： 杂志文章,多中心研究,随机对照试验

    doi：10.1111/j.1365-2141.2010.08227.x

    authors： Kerkhoffs JL,van Putten WL,Novotny VM,Te Boekhorst PA,Schipperus MR,Zwaginga JJ,van Pampus LC,de Greef GE,Luten M,Huijgens PC,Brand A,van Rhenen DJ,Dutch - Belgian HOVON cooperative group.

    更新日期：2010-07-01 00:00:00

  • Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis.

    abstract：:Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2008.07227.x

    authors： Cavazzini F,Hernandez JA,Gozzetti A,Russo Rossi A,De Angeli C,Tiseo R,Bardi A,Tammiso E,Crupi R,Lenoci MP,Forconi F,Lauria F,Marasca R,Maffei R,Torelli G,Gonzalez M,Martin-Jimenez P,Maria Hernandez J,Rigolin GM,Cune

    更新日期：2008-08-01 00:00:00

  • Mutation in the ATP-binding site of BCR-ABL in a patient with chronic myeloid leukaemia with increasing resistance to STI571.

    abstract：:The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr-...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2002.03708.x

    authors： Barthe C,Gharbi MJ,Lagarde V,Chollet C,Cony-Makhoul P,Reiffers J,Goldman JM,Melo JV,Mahon FX

    更新日期：2002-10-01 00:00:00

  • Haemoglobin oxygen saturation is a determinant of cerebral artery blood flow velocity in children with sickle cell anaemia.

    abstract：:Steady-state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO(...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2009.07652.x

    authors： Quinn CT,Variste J,Dowling MM

    更新日期：2009-05-01 00:00:00