{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:49:15Z","timestamp":1781110155919,"version":"3.54.1"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R35 CA197706"],"award-info":[{"award-number":["R35 CA197706"]}],"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":[[2021,3,16]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The mechanisms that promote the transition from chronic phase to blast crisis (BC) in chronic myeloid leukemia (CML) patients are not fully described. Given the loss of miR-15\/16 loci is critical in the development of myeloid and lymphocytic leukemia, here we evaluated the correlation between the expression of miR-15a\/16 and miR-15b\/16 with the transition of CML from chronic phase to BC. A significant reduction of miR-15a, miR-15b, and miR-16 expression and an overexpression of their targets, such as Bmi-1, ROR1, and Bcl-2, can describe the progression from chronic phase to BC. This study suggests that targeting different oncogenes activated by the same genetic\/epigenetic alteration could represent an important advancement in the treatment of BC CML.<\/jats:p>","DOI":"10.1073\/pnas.2101566118","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T16:26:49Z","timestamp":1615220809000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Loss of expression of both miR-15\/16 loci in CML transition to blast crisis"],"prefix":"10.1073","volume":"118","author":[{"given":"Francesca","family":"Lovat","sequence":"first","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, 2308 NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Nigita","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-9836","authenticated-orcid":false,"given":"Karilyn","family":"Larkin","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"},{"name":"Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9089-8816","authenticated-orcid":false,"given":"Mark D.","family":"Minden","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-1958","authenticated-orcid":false,"given":"Michael","family":"Andreeff","sequence":"additional","affiliation":[{"name":"Section of Molecular Hematology and Therapy, Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-0889","authenticated-orcid":false,"given":"Bing Z.","family":"Carter","sequence":"additional","affiliation":[{"name":"Section of Molecular Hematology and Therapy, Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-1457","authenticated-orcid":false,"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210;"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907153410306"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(87)90754-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199904293401706"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2007.1.384"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-690230"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2634"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242606799"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050995"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.11.019"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514954112"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814980115"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003597117"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61901-7"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1823"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23587"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2552"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506654102"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708264114"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1532\/IJH97.05013"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2014.07.002"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-065599"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504703200"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-105072"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404623"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209734"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3379"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6585957"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag1180"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513257"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-181"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2101566118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2101566118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T08:31:06Z","timestamp":1649838666000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2101566118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,3,16]]}},"alternative-id":["10.1073\/pnas.2101566118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2101566118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]},"assertion":[{"value":"2021-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2101566118"}}