MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera

Abstract Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utili...

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Autores principales:	Chartsiam Tipgomut, Archrob Khuhapinant, Marieangela C. Wilson, Saiphon Poldee, Kate J. Heesom, Chanatip Metheetrairut, Orapan Sripichai, Chalermchai Mitrpant, Jan Frayne, Kongtana Trakarnsanga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b15d64123864b8b8feb2015fea7d143
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spelling	oai:doaj.org-article:5b15d64123864b8b8feb2015fea7d1432021-11-21T12:24:59ZMTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera10.1038/s41598-021-01877-02045-2322https://doaj.org/article/5b15d64123864b8b8feb2015fea7d1432021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01877-0https://doaj.org/toc/2045-2322Abstract Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5′-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients’ erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.Chartsiam TipgomutArchrob KhuhapinantMarieangela C. WilsonSaiphon PoldeeKate J. HeesomChanatip MetheetrairutOrapan SripichaiChalermchai MitrpantJan FrayneKongtana TrakarnsangaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chartsiam Tipgomut Archrob Khuhapinant Marieangela C. Wilson Saiphon Poldee Kate J. Heesom Chanatip Metheetrairut Orapan Sripichai Chalermchai Mitrpant Jan Frayne Kongtana Trakarnsanga MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
description	Abstract Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5′-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients’ erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.
format	article
author	Chartsiam Tipgomut Archrob Khuhapinant Marieangela C. Wilson Saiphon Poldee Kate J. Heesom Chanatip Metheetrairut Orapan Sripichai Chalermchai Mitrpant Jan Frayne Kongtana Trakarnsanga
author_facet	Chartsiam Tipgomut Archrob Khuhapinant Marieangela C. Wilson Saiphon Poldee Kate J. Heesom Chanatip Metheetrairut Orapan Sripichai Chalermchai Mitrpant Jan Frayne Kongtana Trakarnsanga
author_sort	Chartsiam Tipgomut
title	MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
title_short	MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
title_full	MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
title_fullStr	MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
title_full_unstemmed	MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera
title_sort	mtap-related increased erythroblast proliferation as a mechanism of polycythaemia vera
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b15d64123864b8b8feb2015fea7d143
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MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera

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