{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:27:50Z","timestamp":1790072870827,"version":"4.0.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T00:00:00Z","timestamp":1478131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T00:00:00Z","timestamp":1478131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute myeloid leukemia (AML) can display\n                    <jats:italic>de novo<\/jats:italic>\n                    or acquired resistance to cytosine arabinoside (Ara-C), a primary component of induction chemotherapy. To identify genes capable of independently imposing Ara-C resistance, we applied a genome-wide CRISPR library to human U937 cells and exposed to them to Ara-C. Interestingly, all drug resistant clones contained guide RNAs for\n                    <jats:italic>DCK<\/jats:italic>\n                    . To avoid\n                    <jats:italic>DCK<\/jats:italic>\n                    gene modification, gRNA resistant\n                    <jats:italic>DCK<\/jats:italic>\n                    cDNA was created by the introduction of silent mutations. The CRISPR screening was repeated using the gRNA resistant\n                    <jats:italic>DCK<\/jats:italic>\n                    , and loss of\n                    <jats:italic>SLC29A<\/jats:italic>\n                    was identified as also being capable of conveying Ara-C drug resistance. To determine if loss of\n                    <jats:italic>Dck<\/jats:italic>\n                    results in increased sensitivity to other drugs, we conducted a screen of 446 FDA approved drugs using two Dck-defective BXH-2 derived murine AML cell lines and their Ara-C sensitive parental lines. Both cell lines showed an increase in sensitivity to prednisolone. Guide RNA resistant cDNA rescue was a legitimate strategy and multiple\n                    <jats:italic>DCK<\/jats:italic>\n                    or\n                    <jats:italic>SLC29A<\/jats:italic>\n                    deficient human cell clones were established with one clone becoming prednisolone sensitive. Dck-defective leukemic cells may become prednisolone sensitive indicating prednisolone may be an effective adjuvant therapy in some cases of DCK-negative AML.\n                  <\/jats:p>","DOI":"10.1038\/srep36199","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T06:21:31Z","timestamp":1478154091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Using genome-wide CRISPR library screening with library resistant DCK to find new sources of Ara-C drug resistance in AML"],"prefix":"10.1038","volume":"6","author":[{"given":"Morito","family":"Kurata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Rathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natashay J.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie K.","family":"Aumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine M.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Willemijn","family":"Veldhuijzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branden S.","family":"Moriarity","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Largaespada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,3]]},"reference":[{"key":"BFsrep36199_CR1","doi-asserted-by":"publisher","first-page":"4539","DOI":"10.1200\/JCO.2008.16.4293","volume":"26","author":"JP Radich","year":"2008","unstructured":"Radich, J. P. Molecular classification of acute myeloid leukemia: are we there yet? 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Dr. Largaespada is co-owner and advisor to NeoClone Biotechnology, Inc., B-MoGen Biotechnologies Inc., Recombinetics Inc. and Discovery Genomics, Inc. No resources or personnel from either company were involved in this research in any way. The remaining authors declare no competing financial interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36199"}}