{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:37:31Z","timestamp":1790505451105,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"7","license":[{"start":{"date-parts":[[2015,8,2]],"date-time":"2015-08-02T00:00:00Z","timestamp":1438473600000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"name":"NCI","award":["CA81534"],"award-info":[{"award-number":["CA81534"]}]},{"name":"NCI","award":["CA140158"],"award-info":[{"award-number":["CA140158"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,2,17]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    B-cell chronic lymphocytic leukemia (CLL) is the most common adult leukemia. We previously found that dysregulation of the T-cell leukemia\/lymphoma 1 (\n                    <jats:italic>TCL1<\/jats:italic>\n                    ) oncogene is a critical contributing event in the pathogenesis of this disease. In this study we investigated molecular causes of\n                    <jats:italic>TCL1<\/jats:italic>\n                    overexpression in CLL. We identified\n                    <jats:italic>miR-3676<\/jats:italic>\n                    as a powerful regulator of\n                    <jats:italic>TCL1<\/jats:italic>\n                    expression. We found that\n                    <jats:italic>miR-3676<\/jats:italic>\n                    is down-regulated on all groups of CLLs and mutated in 1% of CLLs. Interestingly,\n                    <jats:italic>miR-3676<\/jats:italic>\n                    is located at 17p13, only 500-kb centromeric of tumor protein p53 (\n                    <jats:italic>Tp53<\/jats:italic>\n                    ), and is codeleted with\n                    <jats:italic>Tp53<\/jats:italic>\n                    in 17p-deleted CLL. Loss of\n                    <jats:italic>miR-3676<\/jats:italic>\n                    causes high levels of\n                    <jats:italic>TCL1<\/jats:italic>\n                    expression contributing to CLL progression. Thus, this study uncovers a major mechanism in the pathogenesis of CLL.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1500010112","type":"journal-article","created":{"date-parts":[[2015,2,2]],"date-time":"2015-02-02T23:18:45Z","timestamp":1422919125000},"page":"2169-2174","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["<i>TCL1<\/i>\n                    targeting\n                    <i>miR-3676<\/i>\n                    is codeleted with tumor protein p53 in chronic lymphocytic leukemia"],"prefix":"10.1073","volume":"112","author":[{"given":"Veronica","family":"Balatti","sequence":"first","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Rizzotto","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecelia","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Palamarchuk","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fadda","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosantony","family":"Pandolfo","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"},{"name":"Department of Health Sciences, University \u201cMagna Grecia\u201d of Catanzaro, Catanzaro 88100, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Z.","family":"Rassenti","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Hertlein","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arletta","family":"Lozanski","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Lozanski","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Pekarsky","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Immunology and Medical Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,2,2]]},"reference":[{"key":"e_1_3_3_1_2","unstructured":"M Sgambati M Linet S Devesa Chronic Lymphocytic Leukemia Epidemiological Familial and Genetic Aspects. 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