{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:30:09Z","timestamp":1791419409642,"version":"4.3.3"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"7642","license":[{"start":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T00:00:00Z","timestamp":1486944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T00:00:00Z","timestamp":1486944000000},"content-version":"vor","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":[[2017,2,23]]},"DOI":"10.1038\/nature21076","type":"journal-article","created":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T10:31:12Z","timestamp":1486722672000},"page":"479-483","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":236,"title":["Metabolic gatekeeper function of B-lymphoid transcription factors"],"prefix":"10.1038","volume":"542","author":[{"given":"Lai N.","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Braas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Woong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadriye Nehir","family":"Cosgun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hurtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedmehdi","family":"Shojaee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Cazzaniga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Schjerven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Kornblau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Konopleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles A.","family":"Pufall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace J.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Milne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Phillip","family":"Koeffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora S.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Borkhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross A.","family":"Dickins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Graeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"M\u00fcschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,13]]},"reference":[{"key":"BFnature21076_CR1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/44076","volume":"401","author":"SL Nutt","year":"1999","unstructured":"Nutt, S. L., Heavey, B., Rolink, A. G. & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401, 556\u2013562 (1999)","journal-title":"Nature"},{"key":"BFnature21076_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0092-8674(94)90407-3","volume":"79","author":"K Georgopoulos","year":"1994","unstructured":"Georgopoulos, K. et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell 79, 143\u2013156 (1994)","journal-title":"Cell"},{"key":"BFnature21076_CR3","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nature05690","volume":"446","author":"CG Mullighan","year":"2007","unstructured":"Mullighan, C. G. et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446, 758\u2013764 (2007)","journal-title":"Nature"},{"key":"BFnature21076_CR4","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature06866","volume":"453","author":"CG Mullighan","year":"2008","unstructured":"Mullighan, C. G. et al. BCR\u2013ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453, 110\u2013114 (2008)","journal-title":"Nature"},{"key":"BFnature21076_CR5","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nature09571","volume":"468","author":"D Nakada","year":"2010","unstructured":"Nakada, D., Saunders, T. L. & Morrison, S. J. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 468, 653\u2013658 (2010)","journal-title":"Nature"},{"key":"BFnature21076_CR6","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nature09595","volume":"468","author":"B Gan","year":"2010","unstructured":"Gan, B. et al. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468, 701\u2013704 (2010)","journal-title":"Nature"},{"key":"BFnature21076_CR7","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nature09572","volume":"468","author":"S Gurumurthy","year":"2010","unstructured":"Gurumurthy, S. et al. The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 468, 659\u2013663 (2010)","journal-title":"Nature"},{"key":"BFnature21076_CR8","doi-asserted-by":"publisher","first-page":"4172","DOI":"10.1172\/JCI63377","volume":"122","author":"TC Brennan-Speranza","year":"2012","unstructured":"Brennan-Speranza, T. C. et al. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J. Clin. Invest. 122, 4172\u20134189 (2012)","journal-title":"J. Clin. Invest."},{"key":"BFnature21076_CR9","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1016\/j.molcel.2013.01.035","volume":"49","author":"N Wu","year":"2013","unstructured":"Wu, N. et al. AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1. Mol. Cell 49, 1167\u20131175 (2013)","journal-title":"Mol. Cell"},{"key":"BFnature21076_CR10","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.phrs.2009.04.004","volume":"60","author":"R Nogueiras","year":"2009","unstructured":"Nogueiras, R. et al. The endocannabinoid system: role in glucose and energy metabolism. Pharmacol. Res. 60, 93\u201398 (2009)","journal-title":"Pharmacol. Res"},{"key":"BFnature21076_CR11","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.devcel.2004.08.006","volume":"7","author":"KL Medina","year":"2004","unstructured":"Medina, K. L. et al. Assembling a gene regulatory network for specification of the B cell fate. Dev. Cell 7, 607\u2013617 (2004)","journal-title":"Dev. Cell"},{"key":"BFnature21076_CR12","doi-asserted-by":"publisher","first-page":"17016","DOI":"10.1073\/pnas.1112169108","volume":"108","author":"A Di Tullio","year":"2011","unstructured":"Di Tullio, A. et al. CCAAT\/enhancer binding protein alpha (C\/EBP\u03b1)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation. Proc. Natl Acad. Sci. USA 108, 17016\u201317021 (2011)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature21076_CR13","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1210\/en.2009-0987","volume":"151","author":"JA Fretz","year":"2010","unstructured":"Fretz, J. A. et al. Altered metabolism and lipodystrophy in the early B-cell factor 1-deficient mouse. Endocrinology 151, 1611\u20131621 (2010)","journal-title":"Endocrinology"},{"key":"BFnature21076_CR14","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1097-2765(00)80306-8","volume":"3","author":"Z Wu","year":"1999","unstructured":"Wu, Z. et al. Cross-regulation of C\/EBP\u03b1 and PPAR\u03b3 controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol. Cell 3, 151\u2013158 (1999)","journal-title":"Mol. Cell"},{"key":"BFnature21076_CR15","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1073\/pnas.0308061100","volume":"101","author":"RJ Shaw","year":"2004","unstructured":"Shaw, R. J. et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc. Natl Acad. Sci. USA 101, 3329\u20133335 (2004)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature21076_CR16","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1158\/2159-8290.CD-15-0892","volume":"5","author":"A Mart\u00edn-Lorenzo","year":"2015","unstructured":"Mart\u00edn-Lorenzo, A. et al. Infection exposure is a causal factor in B-cell precursor acute lymphoblastic leukemia as a result of Pax5-inherited susceptibility. Cancer Discov. 5, 1328\u20131343 (2015)","journal-title":"Cancer Discov"},{"key":"BFnature21076_CR17","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.cmet.2012.12.001","volume":"17","author":"B Faubert","year":"2013","unstructured":"Faubert, B. et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab. 17, 113\u2013124 (2013)","journal-title":"Cell Metab"},{"key":"BFnature21076_CR18","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1172\/JCI13505","volume":"108","author":"G Zhou","year":"2001","unstructured":"Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167\u20131174 (2001)","journal-title":"J. Clin. Invest."},{"key":"BFnature21076_CR19","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.cell.2014.09.029","volume":"159","author":"LA Gilbert","year":"2014","unstructured":"Gilbert, L. A. et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159, 647\u2013661 (2014)","journal-title":"Cell"},{"key":"BFnature21076_CR20","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1056\/NEJMra052603","volume":"354","author":"CH Pui","year":"2006","unstructured":"Pui, C. H. & Evans, W. E. Treatment of acute lymphoblastic leukemia. N. Engl. J. Med. 354, 166\u2013178 (2006)","journal-title":"N. Engl. J. Med"},{"key":"BFnature21076_CR21","doi-asserted-by":"publisher","first-page":"14228","DOI":"10.1073\/pnas.96.25.14228","volume":"96","author":"L Hanus","year":"1999","unstructured":"Hanus, L. et al. HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor. Proc. Natl Acad. Sci. USA 96, 14228\u201314233 (1999)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature21076_CR22","doi-asserted-by":"publisher","first-page":"38027","DOI":"10.1074\/jbc.M111.275503","volume":"286","author":"CA Stoltzman","year":"2011","unstructured":"Stoltzman, C. A., Kaadige, M. R., Peterson, C. W. & Ayer, D. E. MondoA senses non-glucose sugars: regulation of thioredoxin-interacting protein (TXNIP) and the hexose transport curb. J. Biol. Chem. 286, 38027\u201338034 (2011)","journal-title":"J. Biol. Chem."},{"key":"BFnature21076_CR23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.celrep.2013.08.037","volume":"5","author":"SB Foley","year":"2013","unstructured":"Foley, S. B. et al. Expression of BCR\/ABL p210 from a knockin allele enhances bone marrow engraftment without inducing neoplasia. Cell Rep. 5, 51\u201360 (2013)","journal-title":"Cell Rep"},{"key":"BFnature21076_CR24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/ng.2874","volume":"46","author":"E Papaemmanuil","year":"2014","unstructured":"Papaemmanuil, E. et al. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6\u2013RUNX1 acute lymphoblastic leukemia. Nat. Genet. 46, 116\u2013125 (2014)","journal-title":"Nat. Genet"},{"key":"BFnature21076_CR25","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/ni.3160","volume":"16","author":"S Swaminathan","year":"2015","unstructured":"Swaminathan, S. et al. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat. Immunol. 16, 766\u2013774 (2015)","journal-title":"Nat. Immunol"},{"key":"BFnature21076_CR26","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1182\/blood-2011-07-366542","volume":"118","author":"G Cazzaniga","year":"2011","unstructured":"Cazzaniga, G. et al. Developmental origins and impact of BCR\u2013ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph+ acute lymphoblastic leukemia. Blood 118, 5559\u20135564 (2011)","journal-title":"Blood"},{"key":"BFnature21076_CR27","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1016\/S0140-6736(99)09403-9","volume":"354","author":"JL Wiemels","year":"1999","unstructured":"Wiemels, J. L. et al. Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 354, 1499\u20131503 (1999)","journal-title":"Lancet"},{"key":"BFnature21076_CR28","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1182\/blood.V92.9.3362","volume":"92","author":"S Bose","year":"1998","unstructured":"Bose, S., Deininger, M., Gora-Tybor, J., Goldman, J. M. & Melo, J. V. The presence of typical and atypical BCR\u2013ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood 92, 3362\u20133367 (1998)","journal-title":"Blood"},{"key":"BFnature21076_CR29","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1158\/2159-8290.CD-14-0104","volume":"4","author":"F Damm","year":"2014","unstructured":"Damm, F. et al. Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov. 4, 1088\u20131101 (2014)","journal-title":"Cancer Discov"},{"key":"BFnature21076_CR30","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1084\/jem.189.9.1399","volume":"189","author":"S Li","year":"1999","unstructured":"Li, S., Ilaria, R. L., Jr, Million, R. P., Daley, G. Q. & Van Etten, R. A. The P190, P210, and P230 forms of the BCR\/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J. Exp. Med. 189, 1399\u20131412 (1999)","journal-title":"J. Exp. Med."},{"key":"BFnature21076_CR31","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S0092-8674(04)00419-2","volume":"117","author":"H Xie","year":"2004","unstructured":"Xie, H., Ye, M., Feng, R. & Graf, T. Stepwise reprogramming of B cells into macrophages. Cell 117, 663\u2013676 (2004)","journal-title":"Cell"},{"key":"BFnature21076_CR32","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nature14136","volume":"517","author":"S Konermann","year":"2015","unstructured":"Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR\u2013Cas9 complex. Nature 517, 583\u2013588 (2015)","journal-title":"Nature"},{"key":"BFnature21076_CR33","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/ni.2210","volume":"13","author":"K Ochiai","year":"2012","unstructured":"Ochiai, K. et al. A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation. Nat. Immunol. 13, 300\u2013307 (2012)","journal-title":"Nat. Immunol"},{"key":"BFnature21076_CR34","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.cmet.2014.03.009","volume":"19","author":"M Thai","year":"2014","unstructured":"Thai, M. et al. Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication. Cell Metab. 19, 694\u2013701 (2014)","journal-title":"Cell Metab"},{"key":"BFnature21076_CR35","doi-asserted-by":"publisher","first-page":"4874","DOI":"10.1182\/blood-2009-08-239681","volume":"116","author":"RC Harvey","year":"2010","unstructured":"Harvey, R. C. et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood 116, 4874\u20134884 (2010)","journal-title":"Blood"},{"key":"BFnature21076_CR36","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1182\/blood-2009-05-218560","volume":"115","author":"H Kang","year":"2010","unstructured":"Kang, H. et al. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood 115, 1394\u20131405 (2010)","journal-title":"Blood"},{"key":"BFnature21076_CR37","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1101\/gad.240416.114","volume":"28","author":"GJ Liu","year":"2014","unstructured":"Liu, G. J. et al. Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia. Genes Dev. 28, 1337\u20131350 (2014)","journal-title":"Genes Dev"},{"key":"BFnature21076_CR38","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/ng.2532","volume":"45","author":"L Holmfeldt","year":"2013","unstructured":"Holmfeldt, L. et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat. Genet. 45, 242\u2013252 (2013)","journal-title":"Nat. Genet"}],"updated-by":[{"DOI":"10.1038\/s41586-018-0164-5","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T00:00:00Z","timestamp":1527638400000}}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature21076.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature21076","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature21076.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:59:10Z","timestamp":1684418350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature21076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,13]]},"references-count":38,"journal-issue":{"issue":"7642","published-print":{"date-parts":[[2017,2,23]]}},"alternative-id":["BFnature21076"],"URL":"https:\/\/doi.org\/10.1038\/nature21076","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727298064.793533450","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,13]]},"assertion":[{"value":"3 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the\n                      NR3C1\n                      plot of Fig. 3c (left) of this Letter, the curves for\n                      TXNIP\n                      (middle) were inadvertently plotted. This has been corrected online, and see Supplementary Information to the Amendment for the original Fig. 3c.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}