Detection of erythropoietin receptor mutations in patients with myeloproliferative disorders
Detection of erythropoietin receptor mutations in patients with myeloproliferative disorders
The erythropoietin receptor (EpoR) has been widely studied in murine and human erythropoiesis and a constitutively activated form of the murine receptor (R129C) has been shown to cause erythrocytosis and thrombocytosis indicating that the EpoR and EpoR signalling pathway is involved in both erythropoiesis and thrombopoiesis. The murine receptor can be activated by point mutations in the extracellular domain, truncation of the cytoplasmic domain or by binding to the env product of the Friend Spleen Focus Forming Virus (gp55). Hence, research has been conducted to identify similar activating mutations of the human EpoR in haematological diseases involving the erythroid and myeloid cell lineages.
Myeloproliferative disorders (MPDs) are examples of such diseases and are characterised by the overproduction of erythrocytes, granulocytes and platelets. EpoR genomic and mRNA sequences were examined from bone marrow and platelet samples from 12 MPD patients using the polymerase chain reaction, restriction digest analysis and DNA sequencing but no EpoR mutations were detected.
MPD patients produce endogenous erythroid colonies (EEC) in vitro which are capable of differentiation and proliferation in the absence of an exogenous source of erythropoietin (Epo). EEC formation is a common feature of MPDs but has never been reported in the myelodysplastic syndromes (MDS) which are characterised by ineffective haemopoiesis. Erythroid progenitor cells were cultured in the presence and absence of an exogenous source of Epo from MPO patients and also from patients who exhibited thrombocytosis and sideroblastic anaemia and thus had symptoms of both myeloproliferative and myelodysplastic disease (MPD/MDS). MPD patients demonstrated characteristic EEC formation but unexpectedly the patients with thrombocytosis and sideroblastic anaemia also displayed EEC formation.
University of Southampton
White, Helen Elizabeth
4b8c2b75-6e9c-4fd8-83d0-f34afb6732b5
1996
White, Helen Elizabeth
4b8c2b75-6e9c-4fd8-83d0-f34afb6732b5
White, Helen Elizabeth
(1996)
Detection of erythropoietin receptor mutations in patients with myeloproliferative disorders.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The erythropoietin receptor (EpoR) has been widely studied in murine and human erythropoiesis and a constitutively activated form of the murine receptor (R129C) has been shown to cause erythrocytosis and thrombocytosis indicating that the EpoR and EpoR signalling pathway is involved in both erythropoiesis and thrombopoiesis. The murine receptor can be activated by point mutations in the extracellular domain, truncation of the cytoplasmic domain or by binding to the env product of the Friend Spleen Focus Forming Virus (gp55). Hence, research has been conducted to identify similar activating mutations of the human EpoR in haematological diseases involving the erythroid and myeloid cell lineages.
Myeloproliferative disorders (MPDs) are examples of such diseases and are characterised by the overproduction of erythrocytes, granulocytes and platelets. EpoR genomic and mRNA sequences were examined from bone marrow and platelet samples from 12 MPD patients using the polymerase chain reaction, restriction digest analysis and DNA sequencing but no EpoR mutations were detected.
MPD patients produce endogenous erythroid colonies (EEC) in vitro which are capable of differentiation and proliferation in the absence of an exogenous source of erythropoietin (Epo). EEC formation is a common feature of MPDs but has never been reported in the myelodysplastic syndromes (MDS) which are characterised by ineffective haemopoiesis. Erythroid progenitor cells were cultured in the presence and absence of an exogenous source of Epo from MPO patients and also from patients who exhibited thrombocytosis and sideroblastic anaemia and thus had symptoms of both myeloproliferative and myelodysplastic disease (MPD/MDS). MPD patients demonstrated characteristic EEC formation but unexpectedly the patients with thrombocytosis and sideroblastic anaemia also displayed EEC formation.
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Published date: 1996
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Local EPrints ID: 459975
URI: http://eprints.soton.ac.uk/id/eprint/459975
PURE UUID: 041df86d-8462-4bcf-a172-6fe77263f36c
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Date deposited: 04 Jul 2022 17:32
Last modified: 23 Jul 2022 00:58
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Author:
Helen Elizabeth White
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