{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:40:41Z","timestamp":1791222041261,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL128173,CA159203,DK132812"],"award-info":[{"award-number":["HL128173,CA159203,DK132812"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM142634"],"award-info":[{"award-number":["R35GM142634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008258","name":"Hyundai Hope On Wheels","doi-asserted-by":"crossref","award":["Pathophysiology of human CSF3R isoforms in a leukemia predisposition syndrome."],"award-info":[{"award-number":["Pathophysiology of human CSF3R isoforms in a leukemia predisposition syndrome."]}],"id":[{"id":"10.13039\/100008258","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016935","name":"Lisa Dean Moseley Foundation","doi-asserted-by":"crossref","award":["Senescence"],"award-info":[{"award-number":["Senescence"]}],"id":[{"id":"10.13039\/100016935","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016935","name":"Lisa Dean Moseley Foundation","doi-asserted-by":"crossref","award":["Loss of Exocrine Pancreatic Stem Cells"],"award-info":[{"award-number":["Loss of Exocrine Pancreatic Stem Cells"]}],"id":[{"id":"10.13039\/100016935","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Association for Shwachman-Diamond Syndrome","award":["3\/2024"],"award-info":[{"award-number":["3\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:p>\n                    Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases of SDS result from biallelic mutations in Shwachman-Bodian-Diamond syndrome (SBDS). SBDS interacts with elongation factor\u2013like 1 (EFL1) to displace eukaryotic initiation factor 6 (EIF6) from the 60S ribosomal subunit. Released EIF6 permits the assembly of ribosomal large and small subunits in the cytoplasm. Decreased EIF6 levels due to haploinsufficiency or missense mutations, which lead to decreased protein expression, may provide a somatic genetic rescue and antileukemic effects. We observed accumulation of EIF6 protein in\n                    <jats:italic>sbds<\/jats:italic>\n                    -KO zebrafish models, confirmed this accumulation in patient-derived tissues, and correlated these with changes in ribosomal proteins and tumor protein p53 (TP53) pathways. The mechanism of action for this adaptive response is unknown. To address this, we generated\n                    <jats:italic>eif6<\/jats:italic>\n                    -KO zebrafish, which do not survive more than 10 days after fertilization. We also created 2 mutants with low Eif6 expression, i.e., 5%\u201325% of WT levels, that could survive until adulthood. We bred them with\n                    <jats:italic>sbds<\/jats:italic>\n                    -null strains and analyzed their phenotype and biochemical properties. Low Eif6 levels reduced Tp53 pathway activation but did not rescue neutropenia in Sbds-deficient zebrafish. Further studies elucidating the interplay between SBDS, EIF6, and TP53 and cellular stress responses offer promising insights into SDS pathogenesis, somatic genetic rescue, and therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1172\/jci187778","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T12:00:31Z","timestamp":1739880031000},"source":"Crossref","is-referenced-by-count":8,"title":["Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-7945","authenticated-orcid":true,"given":"Usua","family":"Oyarbide","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Bezzerri","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy."},{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Staton","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Boni","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4036-9772","authenticated-orcid":true,"given":"Arish","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Biology and David H. 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