{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T01:10:18Z","timestamp":1791681018389,"version":"4.3.4"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"7689","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2018,1]]},"DOI":"10.1038\/nature25186","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T10:38:31Z","timestamp":1516185511000},"page":"511-514","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia"],"prefix":"10.1038","volume":"553","author":[{"given":"Gannie","family":"Tzoneva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea L.","family":"Dieck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ambesi-Impiombato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"S\u00e1nchez-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chioma J.","family":"Madubata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Khiabanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esme","family":"Waanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Iacobucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Sulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Paganin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Basso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Gastier-Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mignon L.","family":"Loh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Kirschner-Schwabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Mullighan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Rabadan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo A.","family":"Ferrando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"BFnature25186_CR1","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1056\/NEJMra1400972","volume":"373","author":"SP Hunger","year":"2015","unstructured":"Hunger, S. P. & Mullighan, C. G. Acute lymphoblastic leukemia in children. N. Engl. J. Med. 373, 1541\u20131552 (2015)","journal-title":"N. Engl. J. Med."},{"key":"BFnature25186_CR2","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nm.3078","volume":"19","author":"G Tzoneva","year":"2013","unstructured":"Tzoneva, G. et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat. Med. 19, 368\u2013371 (2013)","journal-title":"Nat. Med."},{"key":"BFnature25186_CR3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/ng.2558","volume":"45","author":"JA Meyer","year":"2013","unstructured":"Meyer, J. A. et al. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat. Genet. 45, 290\u2013294 (2013)","journal-title":"Nat. Genet."},{"key":"BFnature25186_CR4","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1038\/leu.2011.93","volume":"25","author":"B Gerby","year":"2011","unstructured":"Gerby, B. et al. Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations. Leukemia 25, 1249\u20131258 (2011)","journal-title":"Leukemia"},{"key":"BFnature25186_CR5","doi-asserted-by":"publisher","first-page":"3287","DOI":"10.1182\/blood-2008-04-154187","volume":"113","author":"CV Cox","year":"2009","unstructured":"Cox, C. V., Diamanti, P., Evely, R. S., Kearns, P. R. & Blair, A. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood 113, 3287\u20133296 (2009)","journal-title":"Blood"},{"key":"BFnature25186_CR6","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1038\/sj.leu.2402608","volume":"16","author":"M Konopleva","year":"2002","unstructured":"Konopleva, M. et al. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia 16, 1713\u20131724 (2002)","journal-title":"Leukemia"},{"key":"BFnature25186_CR7","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nature19801","volume":"538","author":"ED Hawkins","year":"2016","unstructured":"Hawkins, E. D. et al. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature 538, 518\u2013522 (2016)","journal-title":"Nature"},{"key":"BFnature25186_CR8","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1126\/science.1164266","volume":"322","author":"CG Mullighan","year":"2008","unstructured":"Mullighan, C. G. et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 322, 1377\u20131380 (2008)","journal-title":"Science"},{"key":"BFnature25186_CR9","doi-asserted-by":"publisher","first-page":"6604","DOI":"10.1038\/ncomms7604","volume":"6","author":"X Ma","year":"2015","unstructured":"Ma, X. et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat. Commun. 6, 6604 (2015)","journal-title":"Nat. Commun."},{"key":"BFnature25186_CR10","doi-asserted-by":"publisher","first-page":"11306","DOI":"10.1073\/pnas.1608420113","volume":"113","author":"K Oshima","year":"2016","unstructured":"Oshima, K. et al. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. Proc. Natl Acad. Sci. USA 113, 11306\u201311311 (2016)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25186_CR11","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nm.3840","volume":"21","author":"B Li","year":"2015","unstructured":"Li, B. et al. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat. Med. 21, 563\u2013571 (2015)","journal-title":"Nat. Med."},{"key":"BFnature25186_CR12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature09727","volume":"471","author":"CG Mullighan","year":"2011","unstructured":"Mullighan, C. G. et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 471, 235\u2013239 (2011)","journal-title":"Nature"},{"key":"BFnature25186_CR13","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1038\/leu.2015.107","volume":"29","author":"K Malinowska-Ozdowy","year":"2015","unstructured":"Malinowska-Ozdowy, K. et al. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia. Leukemia 29, 1656\u20131667 (2015)","journal-title":"Leukemia"},{"key":"BFnature25186_CR14","doi-asserted-by":"crossref","first-page":"18759","DOI":"10.1016\/S0021-9258(18)37348-4","volume":"263","author":"J Spycha\u0142a","year":"1988","unstructured":"Spycha\u0142a, J., Madrid-Marina, V. & Fox, I. H. High Km soluble 5\u2032-nucleotidase from human placenta. Properties and allosteric regulation by IMP and ATP. J. Biol. Chem. 263, 18759\u201318765 (1988)","journal-title":"J. Biol. Chem."},{"key":"BFnature25186_CR15","doi-asserted-by":"publisher","first-page":"6185","DOI":"10.1074\/jbc.M007623200","volume":"276","author":"C Gazziola","year":"2001","unstructured":"Gazziola, C., Ferraro, P., Moras, M., Reichard, P. & Bianchi, V. Cytosolic high Km 5\u2032-nucleotidase and 5\u2032(3\u2032)-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism. J. Biol. Chem. 276, 6185\u20136190 (2001)","journal-title":"J. Biol. Chem."},{"key":"BFnature25186_CR16","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cccn.2005.05.006","volume":"361","author":"C Brouwer","year":"2005","unstructured":"Brouwer, C. et al. Role of 5\u2032-nucleotidase in thiopurine metabolism: enzyme kinetic profile and association with thio-GMP levels in patients with acute lymphoblastic leukemia during 6-mercaptopurine treatment. Clin. Chim. Acta 361, 95\u2013103 (2005)","journal-title":"Clin. Chim. Acta"},{"key":"BFnature25186_CR17","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/30756","volume":"393","author":"EH Schroeter","year":"1998","unstructured":"Schroeter, E. H., Kisslinger, J. A. & Kopan, R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382\u2013386 (1998)","journal-title":"Nature"},{"key":"BFnature25186_CR18","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1038\/nm.3665","volume":"20","author":"D Herranz","year":"2014","unstructured":"Herranz, D. et al. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat. Med. 20, 1130\u20131137 (2014)","journal-title":"Nat. Med."},{"key":"BFnature25186_CR19","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/nm.4410","volume":"23","author":"AA Ferrando","year":"2017","unstructured":"Ferrando, A. A. & L\u00f3pez-Ot\u00edn, C. Clonal evolution in leukemia. Nat. Med. 23, 1135\u20131145 (2017)","journal-title":"Nat. Med."},{"key":"BFnature25186_CR20","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1084\/jem.20110105","volume":"208","author":"E Clappier","year":"2011","unstructured":"Clappier, E. et al. Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse. J. Exp. Med. 208, 653\u2013661 (2011)","journal-title":"J. Exp. Med."},{"key":"BFnature25186_CR21","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1182\/blood-2015-10-677021","volume":"127","author":"TN Wong","year":"2016","unstructured":"Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 127, 893\u2013897 (2016)","journal-title":"Blood"},{"key":"BFnature25186_CR22","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature22993","volume":"547","author":"LI Shlush","year":"2017","unstructured":"Shlush, L. I. et al. Tracing the origins of relapse in acute myeloid leukaemia to stem cells. Nature 547, 104\u2013108 (2017)","journal-title":"Nature"},{"key":"BFnature25186_CR23","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nrmicro2319","volume":"8","author":"DI Andersson","year":"2010","unstructured":"Andersson, D. I. & Hughes, D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat. Rev. Microbiol. 8, 260\u2013271 (2010)","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnature25186_CR24","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nature10762","volume":"481","author":"M Greaves","year":"2012","unstructured":"Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306\u2013313 (2012)","journal-title":"Nature"},{"key":"BFnature25186_CR25","doi-asserted-by":"crossref","unstructured":"Wang, J. et al. Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia. eLife 3, (2014)","DOI":"10.7554\/eLife.02869"},{"key":"BFnature25186_CR26","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1021\/bi0271401","volume":"42","author":"L Gan","year":"2003","unstructured":"Gan, L. et al. The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase. Biochemistry 42, 857\u2013863 (2003)","journal-title":"Biochemistry"},{"key":"BFnature25186_CR27","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature12445","volume":"500","author":"ML Reaves","year":"2013","unstructured":"Reaves, M. L., Young, B. D., Hosios, A. M., Xu, Y. F. & Rabinowitz, J. D. Pyrimidine homeostasis is accomplished by directed overflow metabolism. Nature 500, 237\u2013241 (2013)","journal-title":"Nature"},{"key":"BFnature25186_CR28","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1016\/j.celrep.2016.05.035","volume":"15","author":"Z Ser","year":"2016","unstructured":"Ser, Z. et al. Targeting one carbon metabolism with an antimetabolite disrupts pyrimidine homeostasis and induces nucleotide overflow. Cell Reports 15, 2367\u20132376 (2016)","journal-title":"Cell Reports"},{"key":"BFnature25186_CR29","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/sj.leu.2404258","volume":"20","author":"T Palomero","year":"2006","unstructured":"Palomero, T. et al. CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to gamma-secretase inhibitors. Leukemia 20, 1279\u20131287 (2006)","journal-title":"Leukemia"},{"key":"BFnature25186_CR30","doi-asserted-by":"publisher","first-page":"4804","DOI":"10.1182\/blood-2009-04-217794","volume":"114","author":"EA Kimbrel","year":"2009","unstructured":"Kimbrel, E. A . et al. Systematic in vivo structure-function analysis of p300 in hematopoiesis. Blood 114, 4804\u20134812 (2009)","journal-title":"Blood"},{"key":"BFnature25186_CR31","doi-asserted-by":"publisher","first-page":"3987","DOI":"10.1210\/en.2007-0261","volume":"148","author":"K Guo","year":"2007","unstructured":"Guo, K. et al. Disruption of peripheral leptin signaling in mice results in hyperleptinemia without associated metabolic abnormalities. Endocrinology 148, 3987\u20133997 (2007)","journal-title":"Endocrinology"},{"key":"BFnature25186_CR32","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1038\/nm.3955","volume":"21","author":"D Herranz","year":"2015","unstructured":"Herranz, D. et al. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nat. Med. 21, 1182\u20131189 (2015)","journal-title":"Nat. Med."},{"key":"BFnature25186_CR33","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.ccell.2015.12.013","volume":"29","author":"I Iacobucci","year":"2016","unstructured":"Iacobucci, I. et al. Truncating erythropoietin receptor rearrangements in acute lymphoblastic leukemia. Cancer Cell 29, 186\u2013200 (2016)","journal-title":"Cancer Cell"},{"key":"BFnature25186_CR34","doi-asserted-by":"publisher","first-page":"14508","DOI":"10.1073\/pnas.1208715109","volume":"109","author":"MW Schmitt","year":"2012","unstructured":"Schmitt, M. W. et al. Detection of ultra-rare mutations by next-generation sequencing. Proc. Natl Acad. Sci. USA 109, 14508\u201314513 (2012)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25186_CR35","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1038\/nprot.2014.170","volume":"9","author":"SR Kennedy","year":"2014","unstructured":"Kennedy, S. R. et al. Detecting ultralow-frequency mutations by Duplex Sequencing. Nat. Protoc. 9, 2586\u20132606 (2014)","journal-title":"Nat. Protoc."},{"key":"BFnature25186_CR36","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nrc1299","volume":"4","author":"PA Futreal","year":"2004","unstructured":"Futreal, P. A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177\u2013183 (2004)","journal-title":"Nat. Rev. Cancer"},{"key":"BFnature25186_CR37","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1172\/JCI61269","volume":"122","author":"P Van Vlierberghe","year":"2012","unstructured":"Van Vlierberghe, P. & Ferrando, A. The molecular basis of T cell acute lymphoblastic leukemia. J. Clin. Invest. 122, 3398\u20133406 (2012)","journal-title":"J. Clin. Invest."},{"key":"BFnature25186_CR38","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1182\/blood-2011-03-341412","volume":"118","author":"J Zhang","year":"2011","unstructured":"Zhang, J. et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children\u2019s Oncology Group. Blood 118, 3080\u20133087 (2011)","journal-title":"Blood"},{"key":"BFnature25186_CR39","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","volume":"347","author":"Y Hu","year":"2009","unstructured":"Hu, Y. & Smyth, G. K. ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J. Immunol. Methods 347, 70\u201378 (2009)","journal-title":"J. Immunol. Methods"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature25186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature25186","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nature25186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nature25186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:11:20Z","timestamp":1684433480000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature25186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":39,"journal-issue":{"issue":"7689","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["BFnature25186"],"URL":"https:\/\/doi.org\/10.1038\/nature25186","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"7 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}