Pubblicazioni

Autori:

Cipolli, Marco; Boni, Christian; Penzo, Marianna; Villa, Isabella; Bolamperti, Simona; Baldisseri, Elena; Frattini, Annalisa; Porta, Giovanni; Api, Martina; Selicato, Nora; Roccia, Pamela; Pollutri, Daniela; Marinelli Busilacchi, Elena; Poloni, Antonella; Caporelli, Nicole; D'Amico, Giovanna; Pegoraro, Anna; Cesaro, Simone; Oyarbide, Usua; Vella, Antonio; Lippi, Giuseppe; Corey, Seth J; Valli, Roberto; Polini, Alessandro; Bezzerri, Valentino

Titolo:

Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

A Stampa

Referee:

Sì

Nome rivista:

British Journal of Haematology

ISSN Rivista:

0007-1048

N° Volume:

204

Intervallo pagine:

292-305

Parole chiave:

Shwachman-Diamond syndrome, ataluren, inherited bone marrow failure syndromes, myelodysplastic syndromes

Breve descrizione dei contenuti:

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183-184TA>CT nonsense mutation. Several translational readthrough-inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full-length SBDS protein synthesis in SDS-derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS-derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full-length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation.

Pagina Web:

https://onlinelibrary.wiley.com/doi/10.1111/bjh.19134

Id prodotto:

135820

Handle IRIS:

11562/1110807

ultima modifica:

13 gennaio 2024

Citazione bibliografica:

Cipolli, Marco; Boni, Christian; Penzo, Marianna; Villa, Isabella; Bolamperti, Simona; Baldisseri, Elena; Frattini, Annalisa; Porta, Giovanni; Api, Martina; Selicato, Nora; Roccia, Pamela; Pollutri, Daniela; Marinelli Busilacchi, Elena; Poloni, Antonella; Caporelli, Nicole; D'Amico, Giovanna; Pegoraro, Anna; Cesaro, Simone; Oyarbide, Usua; Vella, Antonio; Lippi, Giuseppe; Corey, Seth J; Valli, Roberto; Polini, Alessandro; Bezzerri, Valentino, Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells «British Journal of Haematology» , vol. 204 , 2024 , pp. 292-305

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