{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:42:32Z","timestamp":1722991352570},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"AIRC 2019","award":["AIRC 2019 [IG 23329]"],"award-info":[{"award-number":["AIRC 2019 [IG 23329]"]}]},{"name":"ANAT","award":["ANAT2019"],"award-info":[{"award-number":["ANAT2019"]}]},{"name":"FESR Lazio Innova","award":["POR 2014-2020- A0375-2020-36524"],"award-info":[{"award-number":["POR 2014-2020- A0375-2020-36524"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Ataxia-telangiectasia (A-T) is a rare autosomal recessive multi-system and life-shortening disease, characterized by progressive cerebellar neurodegeneration, immunodeficiency, radiation sensitivity and cancer predisposition, with high incidence of leukemia and lymphoma. A-T is caused by mutations in the gene encoding for ATM protein that has a major role in maintaining the integrity of the genome. Because there are no cures for A-T, we aimed to tackle immunodeficiency and prevent cancer onset\/progression by transplantation therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Enriched hematopoietic stem\/progenitor cells (HSPCs), collected from bone marrow of wild-type mice, were transplanted in the caudal vein of 1\u00a0month old conditioned <jats:italic>Atm<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Genomic analyses showed that transplanted Atm positive cells were found in lymphoid organs. B cells isolated from spleen of transplanted mice were able to undergo class switching recombination. Thymocytes were capable to correctly differentiate and\u00a0consequently an increase of helper T cells and TCR\u03b2<jats:sup>hi<\/jats:sup> expressing cells was observed. Protein analysis of isolated T and B cells from transplanted mice, revealed that they expressed Atm and responded to DNA damage by initiating an Atm-dependent phosphorylation cascade. Indeed, aberrant metaphases were reduced in transplanted Atm-deficient mice. Six months after transplantation, <jats:italic>Atm<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice showed signs of aging, but they maintained the rescue of T cells maturation, showed DNA damage response, and prevented thymoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We can conclude that wild-type enriched HSPCs transplantation into young Atm-deficient mice can ameliorate A-T hematopoietic phenotypes and prevent tumor of hematopoietic origin.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40164-024-00544-0","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T07:12:21Z","timestamp":1722928341000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hematopoietic stem\/progenitor cell transplantation recovers immune defects and prevents lymphomas in Atm-deficient mice"],"prefix":"10.1186","volume":"13","author":[{"given":"Bruna Sabino Pinho","family":"de Oliveira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Giovinazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Putti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matilde","family":"Merolle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Orsini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe D.","family":"Tocchini-Valentini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Lancrin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Naro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Pellegrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"issue":"3","key":"544_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrc1011","volume":"3","author":"Y Shiloh","year":"2003","unstructured":"Shiloh Y. ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer. 2003;3(3):155\u201368.","journal-title":"Nat Rev Cancer"},{"issue":"9","key":"544_CR2","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1084\/jem.20041162","volume":"200","author":"B Reina-San-Martin","year":"2004","unstructured":"Reina-San-Martin B, Chen HT, Nussenzweig A, Nussenzweig MC. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med. 2004;200(9):1103\u201310.","journal-title":"J Exp Med"},{"issue":"5","key":"544_CR3","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1111\/bjh.17736","volume":"194","author":"S Bakhtiar","year":"2021","unstructured":"Bakhtiar S, Salzmann-Manrique E, Donath H, Woelke S, Duecker RP, Fritzemeyer S, et al. The incidence and type of cancer in patients with ataxia-telangiectasia via a retrospective single-centre study. 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