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A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure

Ammeti, Daniele
•
Marzollo, Antonio
•
Gabelli, Maria
altro
Faleschini, Michela
2023
  • journal article

Periodico
BRITISH JOURNAL OF HAEMATOLOGY
Abstract
MECOM-associated syndrome (MECOM-AS) is a rare disease characterized by amegakaryocytic thrombocytopenia, progressive bone marrow failure, pancytopenia and radioulnar synostosis with high penetrance. The clinical phenotype may also include finger malformations, cardiac and renal alterations, hearing loss, B-cell deficiency and predisposition to infections. The syndrome, usually diagnosed in the neonatal period because of severe thrombocytopenia, is caused by mutations in the MECOM gene, encoding for the transcription factor EVI1. The mechanism linking the alteration of EVI1 function and thrombocytopenia is poorly understood. In a paediatric patient affected by severe thrombocytopenia, we identified a novel variant of the MECOM gene (p.P634L), whose effect was tested on pAP-1 enhancer element and promoters of targeted genes showing that the mutation impairs the repressive activity of the transcription factor. Moreover, we demonstrated that EVI1 controls the transcriptional regulation of MPL, a gene whose mutations are responsible for congenital amegakaryocytic thrombocytopenia (CAMT), potentially explaining the partial overlap between MECOM-AS and CAMT.
DOI
10.1111/bjh.19023
WOS
WOS:001052881900001
Archivio
https://hdl.handle.net/11368/3081104
info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85168711886
https://onlinelibrary.wiley.com/doi/10.1111/bjh.19023
Diritti
open access
FVG url
https://arts.units.it/bitstream/11368/3081104/3/Br J Haematol - 2023 - Ammeti - A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia.pdf
Soggetti
  • EVI1

  • MECOM

  • MECOM-AS

  • MPL

  • bone marrow failure

  • inherited thrombocyto...

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