{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T21:00:21Z","timestamp":1786222821568,"version":"build-2736575974"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2018,3,18]],"date-time":"2018-03-18T00:00:00Z","timestamp":1521331200000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["PO1-CA81534"],"award-info":[{"award-number":["PO1-CA81534"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R35CA197706"],"award-info":[{"award-number":["R35CA197706"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,10,3]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    This study highlights a pathogenic role for loss of\n                    <jats:italic>miR-15\/16<\/jats:italic>\n                    in chronic lymphocytic leukemia (CLL). We find that loss of mi\n                    <jats:italic>R-15\/16<\/jats:italic>\n                    promotes overexpression of\n                    <jats:italic>BCL2<\/jats:italic>\n                    and\n                    <jats:italic>ROR1<\/jats:italic>\n                    , which each factor in leukemia pathogenesis. Treatment with single-agent venetoclcax, which inhibits Bcl2, is highly effective in patients with CLL, but generally cannot eradicate minimal residual disease. Since loss of\n                    <jats:italic>miR-15\/16<\/jats:italic>\n                    also promotes expression of\n                    <jats:italic>ROR1<\/jats:italic>\n                    , we examined the cytotoxic activity of venetoclax in combination with an anti-ROR1 mAb, cirmtuzumab. We found that cirmtuzumab could enhance the in vitro cytotoxicity of venetoclcax for CLL cells with high-level ROR1. This suggests that combining agents that target ROR1 and Bcl2 may be highly effective in the treatment patients with this disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1708264114","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T21:00:20Z","timestamp":1505768420000},"page":"10731-10736","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["<i>MicroRNA<\/i>\n                    dysregulation to identify therapeutic target combinations for chronic lymphocytic leukemia"],"prefix":"10.1073","volume":"114","author":[{"given":"Laura Z.","family":"Rassenti","sequence":"first","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Balatti","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela M.","family":"Ghia","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Palamarchuk","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Tomasello","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fadda","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Pekarsky","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"George F.","family":"Widhopf","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Medical Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,9,18]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"33","volume-title":"Chronic Lymphocytic Leukemias","author":"Sgambati M","year":"2001","unstructured":"M Sgambati, M Linet, S Devesa, Chronic lymphocytic leukemia, epidemiological, familial, and genetic aspects. 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