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Evans Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100008884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"HHS | NIH | National Human Genome Research Institute","doi-asserted-by":"publisher","award":["intramural"],"award-info":[{"award-number":["intramural"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["intramural"],"award-info":[{"award-number":["intramural"]}],"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":[[2018,10,30]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Somatic mutations in some splicing factor genes are frequently found in myelodysplastic syndromes (MDS) and MDS-related acute myeloid leukemia (AML), blood cancers with few effective treatment options. However, the pathophysiological effects of these mutations remain poorly characterized. Here, we report the establishment of mouse models to study a common splicing factor mutation,\n                    <jats:italic>U2AF1<\/jats:italic>\n                    (S34F). Production of the mutant protein in the murine hematopoietic compartment disrupts hematopoiesis in ways resembling human MDS. We further identified deletion of the\n                    <jats:italic>Runx1<\/jats:italic>\n                    gene and other known oncogenic mutations as changes that might collaborate with\n                    <jats:italic>U2af1<\/jats:italic>\n                    (S34F) to give rise to frank AML in mice. However, the\n                    <jats:italic>U2af1<\/jats:italic>\n                    (S34F) mutation was absent in two of the three AML cases, raising the possibility that this mutant protein plays a dispensable role in tumor maintenance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1812669115","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T15:17:35Z","timestamp":1539616655000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Impaired hematopoiesis and leukemia development in mice with a conditional knock-in allele of a mutant splicing factor gene\n                    <i>U2af1<\/i>"],"prefix":"10.1073","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-0584","authenticated-orcid":false,"given":"Dennis Liang","family":"Fei","sequence":"first","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Cancer Biology Section, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhen","sequence":"additional","affiliation":[{"name":"Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Durham","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ferrarone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-918X","authenticated-orcid":false,"given":"Tuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Garrett","sequence":"additional","affiliation":[{"name":"Embryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihide","family":"Yoshimi","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Abdel-Wahab","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065;"},{"name":"Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8046-1063","authenticated-orcid":false,"given":"Robert K.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;"},{"name":"Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Liu","sequence":"additional","affiliation":[{"name":"Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Varmus","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065;"},{"name":"Cancer Biology Section, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"New York Genome Center, New York, NY 10013"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.blre.2005.01.004","article-title":"Myelodysplasic syndromes: A comprehensive review","volume":"19","author":"Catenacci DVT","year":"2005","unstructured":"DVT Catenacci, GJ Schiller, Myelodysplasic syndromes: A comprehensive review. 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Blood 127, 2391\u20132405 (2016).","journal-title":"Blood"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway mutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida K","year":"2011","unstructured":"K Yoshida, , Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478, 64\u201369 (2011).","journal-title":"Nature"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1056\/NEJMoa1103283","article-title":"Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts","volume":"365","author":"Papaemmanuil E","year":"2011","unstructured":"E Papaemmanuil, , Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium 365, 1384\u20131395 (2011).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ng.1031","article-title":"Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes","volume":"44","author":"Graubert TA","year":"2011","unstructured":"TA Graubert, , Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. 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