{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:17:46Z","timestamp":1780431466776,"version":"3.54.1"},"reference-count":50,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic lymphocytic leukemia (CLL) occurs in 2 major forms: aggressive and indolent. Low miR-29b expression in aggressive CLL is associated with poor prognosis. Indiscriminate miR-29b overexpression in the B-lineage of mice causes aberrance, thus warranting the need for selective introduction of miR-29b into B-CLL cells for therapeutic benefit. The oncofetal antigen receptor tyrosine kinase orphan receptor 1 (ROR1) is expressed on malignant B-CLL cells, but not normal B cells, encouraging us with ROR1-targeted delivery for therapeutic miRs. Here, we describe targeted delivery of miR-29b to ROR1+ CLL cells leading to downregulation of DNMT1 and DNMT3A, modulation of global DNA methylation, decreased SP1, and increased p21 expression in cell lines and primary CLL cells in vitro. Furthermore, using an E\u03bc-TCL1 mouse model expressing human ROR1, we report the therapeutic benefit of enhanced survival via cellular reprograming by downregulation of DNMT1 and DNMT3A in vivo. Gene expression profiling of engrafted murine leukemia identified reprogramming of cell cycle regulators with decreased SP1 and increased p21 expression after targeted miR-29b treatment. This finding was confirmed by protein modulation, leading to cell cycle arrest and survival benefit in vivo. Importantly, SP1 knockdown results in p21-dependent compensation of the miR-29b effect on cell cycle arrest. These studies form a basis for leukemic cell\u2013targeted delivery of miR-29b as a promising therapeutic approach for CLL and other ROR1+ B-cell malignancies.<\/jats:p>","DOI":"10.1182\/blood.2018882290","type":"journal-article","created":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T02:36:40Z","timestamp":1559356600000},"page":"432-444","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["ROR1-targeted delivery of miR-29b induces cell cycle arrest and therapeutic benefit in vivo in a CLL mouse model"],"prefix":"10.1182","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0275-9673","authenticated-orcid":false,"given":"Chi-Ling","family":"Chiang","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Comprehensive Cancer Center,"},{"name":"Department of Internal Medicine,"},{"name":"Center for Affordable Nanoengineering of Polymeric Biomedical Devices,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swagata","family":"Goswami","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Comprehensive Cancer Center,"},{"name":"Molecular, Cellular, and Developmental Biology Program,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Frissora","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Comprehensive Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics, College of Pharmacy,"},{"name":"Division of Medicinal Chemistry, College of Pharmacy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearlly S.","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Comprehensive Cancer Center,"},{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Bundschuh","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Department of Physics, and"},{"name":"Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5378-3315","authenticated-orcid":false,"given":"Logan A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Affordable Nanoengineering of Polymeric Biomedical Devices,"},{"name":"Molecular, Cellular, and Developmental Biology Program,"},{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2326-7133","authenticated-orcid":false,"given":"Rajeswaran","family":"Mani","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, College of Medicine,"},{"name":"Comprehensive Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokui M.","family":"Mo","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, The Ohio State University, Columbus, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivasubramanian","family":"Baskar","sequence":"additional","affiliation":[{"name":"Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-3454","authenticated-orcid":false,"given":"Christoph","family":"Rader","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitch A.","family":"Phelps","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center,"},{"name":"Division of Pharmaceutics, College of Pharmacy,"},{"name":"Division of Medicinal Chemistry, College of Pharmacy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Marcucci","sequence":"additional","affiliation":[{"name":"Department of Hematology, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA; 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