{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:41:06Z","timestamp":1791222066812,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T00:00:00Z","timestamp":1518134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Associazione Italiana Sindrome di Shwachman","award":["AISS-2017 to MC and AV"],"award-info":[{"award-number":["AISS-2017 to MC and AV"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Shwachman\u2010Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman\u2010Bodian\u2010Diamond syndrome (<jats:italic>SBDS<\/jats:italic>) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndrome (MDS) and are at higher risk of developing acute myeloid leukemia (AML). Deficiency in <jats:italic>SBDS<\/jats:italic> expression has been associated with increased apoptosis and lack of myeloid differentiation in bone marrow hematopoietic progenitors. Importantly, most SDS patients carry nonsense mutations in <jats:italic>SBDS<\/jats:italic>. Since ataluren is a well\u2010characterized small molecule inhibitor that can suppress nonsense mutations, here, we have assessed the efficacy of this drug in restoring <jats:italic>SBDS<\/jats:italic> expression in hematopoietic cells obtained from a cohort of SDS patients. Remarkably, we show that ataluren treatment readily restores SBDS protein expression in different cell types, particularly bone marrow stem cells. Furthermore, ataluren promotes myeloid differentiation in hematopoietic progenitors, reduces apoptotic rate in primary PBMCs, and brings mammalian target of rapamycin phosphorylation levels back to normal in both lymphoblasts and bone marrow mesenchymal stromal cells (BM\u2010MSCs). Since a specific therapy against SDS is currently lacking, these results provide the rationale for ataluren repurposing clinical trials.<\/jats:p>","DOI":"10.1002\/ajh.25025","type":"journal-article","created":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T06:12:44Z","timestamp":1514527964000},"page":"527-536","source":"Crossref","is-referenced-by-count":24,"title":["Ataluren\u2010driven restoration of Shwachman\u2010Bodian\u2010Diamond syndrome protein function in Shwachman\u2010Diamond syndrome bone marrow cells"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-4487","authenticated-orcid":false,"given":"Valentino","family":"Bezzerri","sequence":"first","affiliation":[{"name":"Department of Medicine University of Verona  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Bardelli","sequence":"additional","affiliation":[{"name":"Unit of Immunology and Immunotherapy, Centro Ricerca Tettamanti, Pediatric Department University of Milano Bicocca, Fondazione MBBM  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Morini","sequence":"additional","affiliation":[{"name":"Department of Physics University of Pavia  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Vella","sequence":"additional","affiliation":[{"name":"Unit of Immunology Azienda Ospedaliera Universitaria Integrata di Verona  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Cesaro","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Hematology Oncology Azienda Ospedaliera Universitaria Integrata di Verona  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-4014","authenticated-orcid":false,"given":"Claudio","family":"Sorio","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Verona  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery University of Milano\u2010Bicocca  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Danesino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-0399","authenticated-orcid":false,"given":"Piero","family":"Farruggia","sequence":"additional","affiliation":[{"name":"Department of Oncology ARNAS Ospedale Civico Palermo  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baroukh Maurice","family":"Assael","sequence":"additional","affiliation":[{"name":"Department of Pulmonology Adult CF center, IRCCS Fondazione C\u00e0 Granda Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"D'amico","sequence":"additional","affiliation":[{"name":"Unit of Immunology and Immunotherapy, Centro Ricerca Tettamanti, Pediatric Department University of Milano Bicocca, Fondazione MBBM  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cipolli","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center Azienda Ospedaliero Universitaria Ospedali Riuniti Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1062"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-735431"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24260"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000055858"},{"issue":"1","key":"e_1_2_8_6_1","first-page":"45","article-title":"Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. 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