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Proteomic landscapes of inherited platelet disorders with different etiologies.
Kreft, Iris C; Huisman, Elise J; Cnossen, Marjon H; van Alphen, Floris P J; van der Zwaan, Carmen; van Leeuwen, Karin; van Spaendonk, Rosalina; Porcelijn, Leendert; Veen, Caroline S B; van den Biggelaar, Maartje; de Haas, Masja; Meijer, Alexander B; Hoogendijk, Arie J.
Afiliação
  • Kreft IC; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands.
  • Huisman EJ; Department of Pediatric Hematology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, The Netherlands; Unit of Transfusion Medicine, Sanquin Blood Supply, Amsterdam, The Netherlands.
  • Cnossen MH; Department of Pediatric Hematology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, The Netherlands.
  • van Alphen FPJ; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands.
  • van der Zwaan C; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands.
  • van Leeuwen K; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands.
  • van Spaendonk R; Department of Immunohematology Diagnostic, Sanquin Diagnostic Services, Amsterdam, The Netherlands; Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, The Netherlands.
  • Porcelijn L; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
  • Veen CSB; Department of Hematology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
  • van den Biggelaar M; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • de Haas M; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; Center for Clinical Transfusion Research, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
  • Meijer AB; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • Hoogendijk AJ; Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands. Electronic address: a.hoogendijk@sanquin.nl.
J Thromb Haemost ; 21(2): 359-372.e3, 2023 02.
Article em En | MEDLINE | ID: mdl-36700500
ABSTRACT

BACKGROUND:

Inherited platelet disorders (IPDs) are a heterogeneous group of rare diseases that are caused by the defects in early megakaryopoiesis, proplatelet formation, and/or mature platelet function. Although genomic sequencing is increasingly used to identify genetic variants underlying IPD, this technique does not disclose resulting molecular changes that impact platelet function. Proteins are the functional units that shape platelet function; however, insights into how variants that cause IPDs impact platelet proteomes are limited.

OBJECTIVES:

The objective of this study was to profile the platelet proteomics signatures of IPDs.

METHODS:

We performed unbiased label-free quantitative mass spectrometry (MS)-based proteome profiling on platelets of 34 patients with IPDs with variants in 13 ISTH TIER1 genes that affect different stages of platelet development.

RESULTS:

In line with the phenotypical heterogeneity between IPDs, proteomes were diverse between IPDs. We observed extensive proteomic alterations in patients with a GFI1B variant and for genetic variants in genes encoding proteins that impact cytoskeletal processes (MYH9, TUBB1, and WAS). Using the diversity between IPDs, we clustered protein dynamics, revealing disrupted protein-protein complexes. This analysis furthermore grouped proteins with similar cellular function and location, classifying mitochondrial protein constituents and identifying both known and putative novel alpha granule associated proteins.

CONCLUSIONS:

With this study, we demonstrate a MS-based proteomics perspective to IPDs. By integrating the effects of IPDs that impact different aspects of platelet function, we dissected the biological contexts of protein alterations to gain further insights into the biology of platelet (dys)function.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos Plaquetários / Proteômica Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos Plaquetários / Proteômica Idioma: En Ano de publicação: 2023 Tipo de documento: Article