{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:09:31Z","timestamp":1773659371033,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1038\/leu.2016.106","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T06:56:40Z","timestamp":1461913000000},"page":"2002-2010","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["\u03b2-Catenin is required for T-cell leukemia initiation and MYC transcription downstream of Notch1"],"prefix":"10.1038","volume":"30","author":[{"given":"C","family":"Gekas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"D\u2019Altri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Aligu\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Bigas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,29]]},"reference":[{"key":"BFleu2016106_CR1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nri2304","volume":"8","author":"I Aifantis","year":"2008","unstructured":"Aifantis I, Raetz E, Buonamici S . Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol 2008; 8: 380\u2013390.","journal-title":"Nat Rev Immunol"},{"key":"BFleu2016106_CR2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1126\/science.1102160","volume":"306","author":"AP Weng","year":"2004","unstructured":"Weng AP, Ferrando AA, Lee W, JPt Morris, Silverman LB, Sanchez-Irizarry C et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269\u2013271.","journal-title":"Science"},{"key":"BFleu2016106_CR3","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1084\/jem.183.5.2283","volume":"183","author":"WS Pear","year":"1996","unstructured":"Pear WS, Aster JC, Scott ML, Hasserjian RP, Soffer B, Sklar J et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated notch alleles. J Exp Med 1996; 183: 2283\u20132291.","journal-title":"J Exp Med"},{"key":"BFleu2016106_CR4","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/dvg.20798","volume":"50","author":"KE Berquam-Vrieze","year":"2012","unstructured":"Berquam-Vrieze KE, Swing DA, Tessarollo L, Dupuy AJ . Characterization of transgenic mice expressing cancer-associated variants of human NOTCH1. Genesis 2012; 50: 112\u2013118.","journal-title":"Genesis"},{"key":"BFleu2016106_CR5","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1172\/JCI35090","volume":"118","author":"MY Chiang","year":"2008","unstructured":"Chiang MY, Xu L, Shestova O, Histen G, L'Heureux S, Romany C et al. Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia. J Clin Invest 2008; 118: 3181\u20133194.","journal-title":"J Clin Invest"},{"key":"BFleu2016106_CR6","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1084\/jem.20070872","volume":"204","author":"BJ Thompson","year":"2007","unstructured":"Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T, Basso G et al. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med 2007; 204: 1825\u20131835.","journal-title":"J Exp Med"},{"key":"BFleu2016106_CR7","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.it.2011.06.005","volume":"32","author":"U Koch","year":"2011","unstructured":"Koch U, Radtke F . Notch in T-ALL: new players in a complex disease. Trends Immunol 2011; 32: 434\u2013442.","journal-title":"Trends Immunol"},{"key":"BFleu2016106_CR8","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1038\/nm1636","volume":"13","author":"T Palomero","year":"2007","unstructured":"Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 2007; 13: 1203\u20131210.","journal-title":"Nat Med"},{"key":"BFleu2016106_CR9","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.ccr.2012.09.016","volume":"22","author":"CM Sawai","year":"2012","unstructured":"Sawai CM, Freund J, Oh P, Ndiaye-Lobry D, Bretz JC, Strikoudis A et al. Therapeutic targeting of the cyclin D3:CDK4\/6 complex in T cell leukemia. Cancer Cell 2012; 22: 452\u2013465.","journal-title":"Cancer Cell"},{"key":"BFleu2016106_CR10","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1084\/jem.20081922","volume":"206","author":"S Gonzalez-Garcia","year":"2009","unstructured":"Gonzalez-Garcia S, Garcia-Peydro M, Martin-Gayo E, Ballestar E, Esteller M, Bornstein R et al. CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7\u2009R{alpha} gene expression in early human thymopoiesis and leukemia. J Exp Med 2009; 206: 779\u2013791.","journal-title":"J Exp Med"},{"key":"BFleu2016106_CR11","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.ccr.2010.08.006","volume":"18","author":"L Espinosa","year":"2010","unstructured":"Espinosa L, Cathelin S, D'Altri T, Trimarchi T, Statnikov A, Guiu J et al. The Notch\/Hes1 pathway sustains NF-kappaB activation through CYLD repression in T cell leukemia. Cancer Cell 2010; 18: 268\u2013281.","journal-title":"Cancer Cell"},{"key":"BFleu2016106_CR12","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.bcmd.2013.07.005","volume":"51","author":"A Bigas","year":"2013","unstructured":"Bigas A, Guiu J, Gama-Norton L . Notch and Wnt signaling in the emergence of hematopoietic stem cells. Blood Cells Mol Dis 2013; 51: 264\u2013270.","journal-title":"Blood Cells Mol Dis"},{"key":"BFleu2016106_CR13","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.cell.2012.05.012","volume":"149","author":"H Clevers","year":"2012","unstructured":"Clevers H, Nusse R . Wnt\/beta-catenin signaling and disease. Cell 2012; 149: 1192\u20131205.","journal-title":"Cell"},{"key":"BFleu2016106_CR14","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.1182\/blood-2006-11-059071","volume":"109","author":"Z Guo","year":"2007","unstructured":"Guo Z, Dose M, Kovalovsky D, Chang R, O'Neil J, Look AT et al. Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation. Blood 2007; 109: 5463\u20135472.","journal-title":"Blood"},{"key":"BFleu2016106_CR15","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1073\/pnas.1315752111","volume":"111","author":"M Dose","year":"2014","unstructured":"Dose M, Emmanuel AO, Chaumeil J, Zhang J, Sun T, Germar K et al. beta-Catenin induces T-cell transformation by promoting genomic instability. Proc Natl Acad Sci USA 2014; 111: 391\u2013396.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2016106_CR16","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0092-8674(01)00336-1","volume":"105","author":"J Huelsken","year":"2001","unstructured":"Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W . beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 2001; 105: 533\u2013545.","journal-title":"Cell"},{"key":"BFleu2016106_CR17","doi-asserted-by":"publisher","first-page":"7551","DOI":"10.1128\/MCB.01034-07","volume":"27","author":"T Fevr","year":"2007","unstructured":"Fevr T, Robine S, Louvard D, Huelsken J . Wnt\/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol 2007; 27: 7551\u20137559.","journal-title":"Mol Cell Biol"},{"key":"BFleu2016106_CR18","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.ccr.2007.11.003","volume":"12","author":"C Zhao","year":"2007","unstructured":"Zhao C, Blum J, Chen A, Kwon HY, Jung SH, Cook JM et al. Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 2007; 12: 528\u2013541.","journal-title":"Cancer Cell"},{"key":"BFleu2016106_CR19","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1126\/science.1186624","volume":"327","author":"Y Wang","year":"2010","unstructured":"Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z et al. The Wnt\/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010; 327: 1650\u20131653.","journal-title":"Science"},{"key":"BFleu2016106_CR20","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1182\/blood-2008-02-138172","volume":"113","author":"F Armstrong","year":"2009","unstructured":"Armstrong F, Brunet de la Grange P, Gerby B, Rouyez MC, Calvo J, Fontenay M et al. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity. Blood 2009; 113: 1730\u20131740.","journal-title":"Blood"},{"key":"BFleu2016106_CR21","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1016\/j.cell.2013.05.041","volume":"153","author":"B King","year":"2013","unstructured":"King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P et al. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell 2013; 153: 1552\u20131566.","journal-title":"Cell"},{"key":"BFleu2016106_CR22","doi-asserted-by":"publisher","first-page":"3917","DOI":"10.1182\/blood-2014-10-609370","volume":"125","author":"V Giambra","year":"2015","unstructured":"Giambra V, Jenkins CE, Lam SH, Hoofd C, Belmonte M, Wang X et al. Leukemia stem cells in T-ALL require active Hif1alpha and Wnt signaling. Blood 2015; 125: 3917\u20133927.","journal-title":"Blood"},{"key":"BFleu2016106_CR23","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nature06933","volume":"453","author":"W Guo","year":"2008","unstructured":"Guo W, Lasky JL, Chang CJ, Mosessian S, Lewis X, Xiao Y et al. Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation. Nature 2008; 453: 529\u2013533.","journal-title":"Nature"},{"key":"BFleu2016106_CR24","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1182\/blood-2012-12-471904","volume":"122","author":"D Kaveri","year":"2013","unstructured":"Kaveri D, Kastner P, Dembele D, Nerlov C, Chan S, Kirstetter P . beta-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL. Blood 2013; 122: 694\u2013704.","journal-title":"Blood"},{"key":"BFleu2016106_CR25","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/nature08020","volume":"459","author":"S Buonamici","year":"2009","unstructured":"Buonamici S, Trimarchi T, Ruocco MG, Reavie L, Cathelin S, Mar BG et al. CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia. Nature 2009; 459: 1000\u20131004.","journal-title":"Nature"},{"key":"BFleu2016106_CR26","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1242\/dev.01558","volume":"132","author":"M Stadtfeld","year":"2005","unstructured":"Stadtfeld M, Graf T . Assessing the role of hematopoietic plasticity for endothelial and hepatocyte development by non-invasive lineage tracing. Development 2005; 132: 203\u2013213.","journal-title":"Development"},{"key":"BFleu2016106_CR27","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1242\/dev.128.8.1253","volume":"128","author":"V Brault","year":"2001","unstructured":"Brault V, Moore R, Kutsch S, Ishibashi M, Rowitch DH, McMahon AP et al. Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 2001; 128: 1253\u20131264.","journal-title":"Development"},{"key":"BFleu2016106_CR28","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.stemcr.2014.04.001","volume":"2","author":"F Aulicino","year":"2014","unstructured":"Aulicino F, Theka I, Ombrato L, Lluis F, Cosma MP . Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1. Stem Cell Rep 2014; 2: 707\u2013720.","journal-title":"Stem Cell Rep"},{"key":"BFleu2016106_CR29","doi-asserted-by":"publisher","first-page":"E4946","DOI":"10.1073\/pnas.1407079111","volume":"111","author":"Y Yashiro-Ohtani","year":"2014","unstructured":"Yashiro-Ohtani Y, Wang H, Zang C, Arnett KL, Bailis W, Ho Y et al. Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proc Natl Acad Sci USA 2014; 111: E4946\u2013E4953.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2016106_CR30","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.cell.2008.10.048","volume":"135","author":"A Wilson","year":"2008","unstructured":"Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 2008; 135: 1118\u20131129.","journal-title":"Cell"},{"key":"BFleu2016106_CR31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1535-6108(03)00334-9","volume":"5","author":"M Lepourcelet","year":"2004","unstructured":"Lepourcelet M, Chen YN, France DS, Wang H, Crews P, Petersen F et al. Small-molecule antagonists of the oncogenic Tcf\/beta-catenin protein complex. Cancer Cell 2004; 5: 91\u2013102.","journal-title":"Cancer Cell"},{"key":"BFleu2016106_CR32","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature14888","volume":"525","author":"CY Fong","year":"2015","unstructured":"Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S, Tyler D et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 2015; 525: 538\u2013542.","journal-title":"Nature"},{"key":"BFleu2016106_CR33","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1126\/science.281.5382.1509","volume":"281","author":"TC He","year":"1998","unstructured":"He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al. Identification of c-MYC as a target of the APC pathway. Science 1998; 281: 1509\u20131512.","journal-title":"Science"},{"key":"BFleu2016106_CR34","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1038\/nm.3665","volume":"20","author":"D Herranz","year":"2014","unstructured":"Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA et al. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med 2014; 20: 1130\u20131137.","journal-title":"Nat Med"},{"key":"BFleu2016106_CR35","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1242\/dev.107714","volume":"142","author":"E Lopez-Arribillaga","year":"2015","unstructured":"Lopez-Arribillaga E, Rodilla V, Pellegrinet L, Guiu J, Iglesias M, Roman AC et al. Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch. Development 2015; 142: 41\u201350.","journal-title":"Development"},{"key":"BFleu2016106_CR36","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1083\/jcb.200904114","volume":"189","author":"K Yamamizu","year":"2010","unstructured":"Yamamizu K, Matsunaga T, Uosaki H, Fukushima H, Katayama S, Hiraoka-Kanie M et al. Convergence of Notch and beta-catenin signaling induces arterial fate in vascular progenitors. J Cell Biol 2010; 189: 325\u2013338.","journal-title":"J Cell Biol"},{"key":"BFleu2016106_CR37","doi-asserted-by":"publisher","first-page":"3553","DOI":"10.1007\/s00018-014-1644-x","volume":"71","author":"GM Collu","year":"2014","unstructured":"Collu GM, Hidalgo-Sastre A, Brennan K . Wnt-Notch signalling crosstalk in development and disease. Cell Mol Life Sci 2014; 71: 3553\u20133567.","journal-title":"Cell Mol Life Sci"},{"key":"BFleu2016106_CR38","doi-asserted-by":"publisher","first-page":"2845","DOI":"10.1182\/blood-2009-07-234377","volume":"115","author":"A Gutierrez","year":"2010","unstructured":"Gutierrez A, Sanda T, Ma W, Zhang J, Grebliunaite R, Dahlberg S et al. Inactivation of LEF1 in T-cell acute lymphoblastic leukemia. Blood 2010; 115: 2845\u20132851.","journal-title":"Blood"},{"key":"BFleu2016106_CR39","doi-asserted-by":"publisher","first-page":"e1001430","DOI":"10.1371\/journal.pbio.1001430","volume":"10","author":"MM Tiemessen","year":"2012","unstructured":"Tiemessen MM, Baert MR, Schonewille T, Brugman MH, Famili F, Salvatori DC et al. The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas. PLoS Biol 2012; 10: e1001430.","journal-title":"PLoS Biol"},{"key":"BFleu2016106_CR40","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.immuni.2012.08.009","volume":"37","author":"S Yu","year":"2012","unstructured":"Yu S, Zhou X, Steinke FC, Liu C, Chen SC, Zagorodna O et al. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 2012; 37: 813\u2013826.","journal-title":"Immunity"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/leu2016106.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2016106","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2016106.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T16:11:26Z","timestamp":1648743086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/leu2016106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,29]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["BFleu2016106"],"URL":"https:\/\/doi.org\/10.1038\/leu.2016.106","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,29]]},"assertion":[{"value":"30 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}