{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:55:32Z","timestamp":1784782532887,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["JP15H01834"],"award-info":[{"award-number":["JP15H01834"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["JP20K12176"],"award-info":[{"award-number":["JP20K12176"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP16H01654"],"award-info":[{"award-number":["JP16H01654"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP18H04992"],"award-info":[{"award-number":["JP18H04992"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Epidemiological studies have revealed a radiation-related increase in the risk of developing acute lymphoblastic leukemia (ALL). Our recent study revealed early induction and increased risk of precursor B-cell (pB) lymphomas in mice after radiation exposure. However, the genomic landscape of radiation-induced B-cell lymphomas remains unclear. To identify the relevant genetic alterations in mice, whole-exome sequencing was performed on both early-onset and late-onset B-cell lymphomas that developed spontaneously or after gamma-irradiation. In addition to multiple driver mutations, the data revealed that interstitial deletion of chromosome 4, including Pax5, and missense mutations in Jak3 are unique genomic alterations in radiation-induced, early-onset B-cell lymphomas. RNA sequencing revealed a pB-cell-type gene-expression profile with no involvement of known fusion genes for human ALLs in the early-onset B-cell lymphomas. Activation of Jak3\/Stat5 signaling in early-onset B-cell lymphomas was validated using western capillary electrophoresis. Those features were similar to those of Philadelphia chromosome-like ALL. Our data suggest a critical role for Pax5 loss-of-function mutations in initiating B-cell leukemogenesis coupled with activation of Jak3\/Stat5 signaling as a basis for the rapid development of radiation-induced pB-ALL. These molecular signatures for radiation-induced cancers will inform both risk assessment and potential targeted therapies for pB-ALL.<\/jats:p>","DOI":"10.1093\/carcin\/bgac034","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T21:12:55Z","timestamp":1649452375000},"page":"693-703","source":"Crossref","is-referenced-by-count":7,"title":["Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome-like acute lymphoblastic leukemia in humans"],"prefix":"10.1093","volume":"43","author":[{"given":"Hirotaka","family":"Tachibana","sequence":"first","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"},{"name":"Department of Biology, Graduate School of Science, Chiba University , Chiba 263-8522 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-4046","authenticated-orcid":false,"given":"Kazuhiro","family":"Daino","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamitsu","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2300-7227","authenticated-orcid":false,"given":"Akira","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Department of Biology, Graduate School of Science, Chiba University , Chiba 263-8522 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-1531","authenticated-orcid":false,"given":"Yoshiya","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"},{"name":"Institute for Environmental Sciences , Aomori 039-3212 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuko","family":"Kakinuma","sequence":"additional","affiliation":[{"name":"Department of Radiation Effects Research, Quantum Medical Science Directorate, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology (QST) , Chiba 263-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"2022083013582039600_CIT0001","first-page":"5","article-title":"Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia.","volume":"5","author":"Portell","year":"2013","journal-title":"Clin. 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