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In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-\u03b3 pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3\u03b2 implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies.<\/jats:p>","DOI":"10.1073\/pnas.1213021110","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T02:09:46Z","timestamp":1356746986000},"page":"1041-1046","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia"],"prefix":"10.1073","volume":"110","author":[{"given":"Qingfei","family":"Jiang","sequence":"first","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Crews","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian L.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Division of Genome Information Sciences, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jung","family":"Chun","sequence":"additional","affiliation":[{"name":"Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada V5Z 1L3;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela C.","family":"Court","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Isquith","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Department of Animal Science, California Polytechnic State University, San Luis Obispo, CA 93405;"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Zipeto","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Department of Health Sciences, University of Milano-Bicocca, 20052 Milan, Italy;"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Goff","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Minden","sequence":"additional","affiliation":[{"name":"Princess Margaret Hospital, Toronto, ON, Canada M5T 2M9;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Sadarangani","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Rusert","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, and"},{"name":"Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim-Hien T.","family":"Dao","sequence":"additional","affiliation":[{"name":"Center for Hematologic Malignancies, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Stem Cell Program, Department of Medicine,"},{"name":"Moores Cancer Center,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S. 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