{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:10:22Z","timestamp":1784855422412,"version":"3.55.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"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":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Evasion of apoptosis is critical for tumorigenesis, and sustained survival of nascent neoplastic cells may depend upon the endogenous levels of pro-survival BCL-2 family members. Indeed, previous studies using gene-targeted mice revealed that BCL-XL, but surprisingly not BCL-2, is critical for the development of c-MYC-induced pre-B\/B lymphomas. However, it remains unclear whether another pro-survival BCL-2 relative contributes to their development. MCL-1 is an intriguing candidate, because it is required for cell survival during early B-lymphocyte differentiation. It is expressed abnormally high in several types of human B-cell lymphomas and is implicated in their resistance to chemotherapy. To test the B-cell intrinsic requirement for endogenous MCL-1 in lymphoma development, we conditionally deleted <jats:italic>Mcl-1<\/jats:italic> in B-lymphoid cells of <jats:italic>E\u03bc-Myc<\/jats:italic> transgenic mice. We found that MCL-1 loss in early B-lymphoid progenitors delayed MYC-driven lymphomagenesis. Moreover, the lymphomas that arose when MCL-1 levels were diminished appeared to have been selected for reduced levels of BIM and\/or increased levels of BCL-XL. These results underscore the importance of MCL-1 in lymphoma development and show that alterations in the levels of other cell death regulators can compensate for deficiencies in MCL-1 expression.<\/jats:p>","DOI":"10.1038\/cddis.2016.43","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T13:50:47Z","timestamp":1457617847000},"page":"e2132-e2132","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Critical B-lymphoid cell intrinsic role of endogenous MCL-1 in c-MYC-induced lymphomagenesis"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-7871","authenticated-orcid":false,"given":"S","family":"Grabow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G L","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A R D","family":"Delbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P N","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Bouillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Strasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,10]]},"reference":[{"key":"BFcddis201643_CR1","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1056\/NEJMra0901217","volume":"361","author":"RS Hotchkiss","year":"2009","unstructured":"Hotchkiss RS, Strasser A, McDunn JE, Swanson PE . Cell death. New Engl J Med 2009; 361: 1570\u20131583.","journal-title":"New Engl J Med"},{"key":"BFcddis201643_CR2","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA . Hallmarks of cancer: the next generation. Cell 2011; 144: 646\u2013674.","journal-title":"Cell"},{"key":"BFcddis201643_CR3","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/0092-8674(91)90362-3","volume":"67","author":"A Strasser","year":"1991","unstructured":"Strasser A, Harris AW, Cory S . Bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 1991; 67: 889\u2013899.","journal-title":"Cell"},{"key":"BFcddis201643_CR4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrm2308","volume":"9","author":"RJ Youle","year":"2008","unstructured":"Youle RJ, Strasser A . The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9: 47\u201359.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis201643_CR5","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrm3722","volume":"15","author":"PE Czabotar","year":"2014","unstructured":"Czabotar PE, Lessene G, Strasser A, Adams JM . Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 2014; 15: 49\u201363.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFcddis201643_CR6","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0092-8674(00)00187-2","volume":"103","author":"DCS Huang","year":"2000","unstructured":"Huang DCS, Strasser A . BH3-only proteins \u2013 essential initiators of apoptotic cell death. Cell 2000; 103: 839\u2013842.","journal-title":"Cell"},{"key":"BFcddis201643_CR7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/sj.cdd.4400998","volume":"9","author":"H Puthalakath","year":"2002","unstructured":"Puthalakath H, Strasser A . Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ 2002; 9: 505\u2013512.","journal-title":"Cell Death Differ"},{"key":"BFcddis201643_CR8","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/cdd.2011.210","volume":"19","author":"F Ke","year":"2012","unstructured":"Ke F, Voss A, Kerr JB, O'Reilly LA, Tai L, Echeverry N et al. BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice. Cell Death Differ 2012; 19: 915\u2013925.","journal-title":"Cell Death Differ"},{"key":"BFcddis201643_CR9","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.tcb.2008.01.007","volume":"18","author":"JE Chipuk","year":"2008","unstructured":"Chipuk JE, Green DR . How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 2008; 18: 157\u2013164.","journal-title":"Trends Cell Biol"},{"key":"BFcddis201643_CR10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1101\/gad.14.1.23","volume":"14","author":"JL Rinkenberger","year":"2000","unstructured":"Rinkenberger JL, Horning S, Klocke B, Roth K, Korsmeyer SJ . Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev 2000; 14: 23\u201327.","journal-title":"Genes Dev"},{"key":"BFcddis201643_CR11","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1126\/science.1106114","volume":"307","author":"J Opferman","year":"2005","unstructured":"Opferman J, Iwasaki H, Ong CC, Suh H, Mizuno S, Akashi K et al. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307: 1101\u20131104.","journal-title":"Science"},{"key":"BFcddis201643_CR12","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nature02067","volume":"426","author":"JT Opferman","year":"2003","unstructured":"Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ . Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 2003; 426: 671\u2013676.","journal-title":"Nature"},{"key":"BFcddis201643_CR13","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1182\/blood-2006-03-013771","volume":"109","author":"I Dzhagalov St","year":"2007","unstructured":"Dzhagalov I St, John A, He YW . The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages. Blood 2007; 109: 1620\u20131626.","journal-title":"Blood"},{"key":"BFcddis201643_CR14","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrc2297","volume":"8","author":"AG Letai","year":"2008","unstructured":"Letai AG . Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer 2008; 8: 121\u2013132.","journal-title":"Nat Rev Cancer"},{"key":"BFcddis201643_CR15","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1038\/sj.onc.1210220","volume":"26","author":"JM Adams","year":"2007","unstructured":"Adams JM, Cory S . The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007; 26: 1324\u20131337.","journal-title":"Oncogene"},{"key":"BFcddis201643_CR16","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.coi.2007.05.004","volume":"19","author":"JM Adams","year":"2007","unstructured":"Adams JM, Cory S . Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol 2007; 19: 488\u2013496.","journal-title":"Curr Opin Immunol"},{"key":"BFcddis201643_CR17","first-page":"175","volume":"166","author":"A Strasser","year":"1990","unstructured":"Strasser A, Harris AW, Vaux DL, Webb E, Bath ML, Adams JM et al. Abnormalities of the immune system induced by dysregulated bcl-2 expression in transgenic mice. Curr Top Microbiol Immunol 1990; 166: 175\u2013181.","journal-title":"Curr Top Microbiol Immunol"},{"key":"BFcddis201643_CR18","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1126\/science.3874430","volume":"228","author":"Y Tsujimoto","year":"1985","unstructured":"Tsujimoto Y, Cossman J, Jaffe E, Croce CM . Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985; 228: 1440\u20131443.","journal-title":"Science"},{"key":"BFcddis201643_CR19","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1126\/science.3929382","volume":"229","author":"Y Tsujimoto","year":"1985","unstructured":"Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM . The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 1985; 229: 1390\u20131393.","journal-title":"Science"},{"key":"BFcddis201643_CR20","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/sj.onc.1208300","volume":"24","author":"H Tagawa","year":"2005","unstructured":"Tagawa H, Karnan S, Suzuki R, Matsuo K, Zhang X, Ota A et al. Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM. Oncogene 2005; 24: 1348\u20131358.","journal-title":"Oncogene"},{"key":"BFcddis201643_CR21","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1182\/blood-2003-07-2469","volume":"103","author":"A Egle","year":"2004","unstructured":"Egle A, Harris AW, Bath ML, O\u2019Reilly L, Cory S . VavP-Bcl2 transgenic mice develop follicular lymphoma preceded by germinal center hyperplasia. Blood 2004; 103: 2276\u20132283.","journal-title":"Blood"},{"key":"BFcddis201643_CR22","doi-asserted-by":"publisher","first-page":"6164","DOI":"10.1073\/pnas.0401471101","volume":"101","author":"A Egle","year":"2004","unstructured":"Egle A, Harris AW, Bouillet P, Cory S . Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci USA 2004; 101: 6164\u20136169.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201643_CR23","doi-asserted-by":"publisher","first-page":"9333","DOI":"10.1073\/pnas.0403286101","volume":"101","author":"MT Hemann","year":"2004","unstructured":"Hemann MT, Zilfou JT, Zhao Z, Burgess DJ, Hannon GJ, Lowe SW . Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci USA 2004; 101: 9333\u20139338.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201643_CR24","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/cdd.2008.195","volume":"16","author":"EM Michalak","year":"2009","unstructured":"Michalak EM, Jansen ES, Happo L, Cragg MS, Tai L, Smyth GK et al. Puma and to a lesser extent Noxa are suppressors of Myc-induced lymphomagenesis. Cell Death Differ 2009; 16: 684\u2013696.","journal-title":"Cell Death Differ"},{"key":"BFcddis201643_CR25","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/348331a0","volume":"348","author":"A Strasser","year":"1990","unstructured":"Strasser A, Harris AW, Bath ML, Cory S . Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 1990; 348: 331\u2013333.","journal-title":"Nature"},{"key":"BFcddis201643_CR26","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1182\/blood-2013-01-475855","volume":"121","author":"CJ Vandenberg","year":"2013","unstructured":"Vandenberg CJ, Cory S . ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia. Blood 2013; 121: 2285\u20132288.","journal-title":"Blood"},{"key":"BFcddis201643_CR27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ccr.2004.07.011","volume":"6","author":"A Letai","year":"2004","unstructured":"Letai A, Sorcinelli MD, Beard C, Korsmeyer SJ . Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell 2004; 6: 241\u2013249.","journal-title":"Cancer Cell"},{"key":"BFcddis201643_CR28","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.1182\/blood-2006-10-051847","volume":"109","author":"PN Kelly","year":"2007","unstructured":"Kelly PN, Puthalakath H, Adams JM, Strasser A . Endogenous bcl-2 is not required for the development of E\u03bc-myc-induced B-cell lymphoma. Blood 2007; 109: 4907\u20134913.","journal-title":"Blood"},{"key":"BFcddis201643_CR29","doi-asserted-by":"publisher","first-page":"6380","DOI":"10.1182\/blood-2011-07-367672","volume":"118","author":"PN Kelly","year":"2011","unstructured":"Kelly PN, Grabow S, Delbridge ARD, Strasser A, Adams JM . Endogenous Bcl-xL is essential for Myc-driven lymphomagenesis in mice. Blood 2011; 118: 6380\u20136386.","journal-title":"Blood"},{"key":"BFcddis201643_CR30","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1038\/onc.2014.132","volume":"34","author":"AR Delbridge","year":"2015","unstructured":"Delbridge AR, Grabow S, Bouillet P, Adams JM, Strasser A . Functional antagonism between pro-apoptotic BIM and anti-apoptotic BCL-XL in MYC-induced lymphomagenesis. Oncogene 2015; 34: 1872\u20131876.","journal-title":"Oncogene"},{"key":"BFcddis201643_CR31","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/nature08822","volume":"463","author":"R Beroukhim","year":"2010","unstructured":"Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J et al. The landscape of somatic copy-number alteration across human cancers. Nature 2010; 463: 899\u2013905.","journal-title":"Nature"},{"key":"BFcddis201643_CR32","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1172\/JCI39964","volume":"120","author":"Z Xiang","year":"2010","unstructured":"Xiang Z, Luo H, Payton JE, Cain J, Ley TJ, Opferman JT et al. Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia. J Clin Invest 2010; 120: 2109\u20132118.","journal-title":"J Clin Invest"},{"key":"BFcddis201643_CR33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1101\/gad.182980.111","volume":"26","author":"SP Glaser","year":"2012","unstructured":"Glaser SP, Lee EF, Trounson E, Bouillet P, Wei A, Fairlie WD et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev 2012; 26: 120\u2013125.","journal-title":"Genes Dev"},{"key":"BFcddis201643_CR34","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1182\/blood-2012-06-440230","volume":"122","author":"B Koss","year":"2013","unstructured":"Koss B, Morrison J, Perciavalle RM, Singh H, Rehg JE, Williams RT et al. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 2013; 122: 1587\u20131598.","journal-title":"Blood"},{"key":"BFcddis201643_CR35","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1101\/gad.232009.113","volume":"28","author":"GL Kelly","year":"2014","unstructured":"Kelly GL, Grabow S, Glaser SP, Fitzsimmons L, Aubrey BJ, Okamoto T et al. Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53. Genes Dev 2014; 28: 58\u201370.","journal-title":"Genes Dev"},{"key":"BFcddis201643_CR36","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.1182\/blood-2015-01-621250","volume":"125","author":"A Delbridge","year":"2015","unstructured":"Delbridge A, Opferman JT, Grabow S, Strasser A . Pro-survival MCL-1 and pro-apoptotic PUMA govern stem\/progenitor cell survival during emergency hematopoiesis. Blood 2015; 125: 3273\u20133280.","journal-title":"Blood"},{"key":"BFcddis201643_CR37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/0092-8674(86)90361-2","volume":"47","author":"WY Langdon","year":"1986","unstructured":"Langdon WY, Harris AW, Cory S, Adams JM . The c-myc oncogene perturbs B lymphocyte development in E\u03bc-myc transgenic mice. Cell 1986; 47: 11\u201318.","journal-title":"Cell"},{"key":"BFcddis201643_CR38","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1084\/jem.167.2.353","volume":"167","author":"AW Harris","year":"1988","unstructured":"Harris AW, Pinkert CA, Crawford M, Langdon WY, Brinster RL, Adams JM . The E\u03bc-myc transgenic mouse: a model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med 1988; 167: 353\u2013371.","journal-title":"J Exp Med"},{"key":"BFcddis201643_CR39","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1093\/nar\/25.6.1317","volume":"25","author":"RC Rickert","year":"1997","unstructured":"Rickert RC, Roes J, Rajewsky K . B lymphocyte-specific, Cre-mediated mutagenesis in mice. Nucleic Acids Res 1997; 25: 1317\u20131318.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis201643_CR40","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1126\/science.1191793","volume":"330","author":"I Vikstrom","year":"2010","unstructured":"Vikstrom I, Carotta S, L\u00fcthje K, Peperzak V, Jost PJ, Glaser S et al. Mcl-1 is essential for germinal center formation and B cell memory. Science 2010; 330: 1095\u20131099.","journal-title":"Science"},{"key":"BFcddis201643_CR41","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1101\/gad.232009.113","volume":"28","author":"GL Kelly","year":"2013","unstructured":"Kelly GL, Grabow S, Glaser SP, Fitzsimmons L, Aubrey BJ, Okamoto T et al. Targeting of MCL-1 kills MYC-driven mouse and human lymphoma cells even when they bear mutations in p53. Genes Dev 2013; 28: 58\u201370.","journal-title":"Genes Dev"},{"key":"BFcddis201643_CR42","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.gde.2009.11.001","volume":"20","author":"L Soucek","year":"2010","unstructured":"Soucek L, Evan GI . The ups and downs of Myc biology. Curr Opin Genetics Dev 2010; 20: 91\u201395.","journal-title":"Curr Opin Genetics Dev"},{"key":"BFcddis201643_CR43","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/0092-8674(92)90123-T","volume":"69","author":"GI Evan","year":"1992","unstructured":"Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 1992; 69: 119\u2013128.","journal-title":"Cell"},{"key":"BFcddis201643_CR44","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1002\/j.1460-2075.1996.tb00756.x","volume":"15","author":"A Strasser","year":"1996","unstructured":"Strasser A, Elefanty AG, Harris AW, Cory S . Progenitor tumours from Em-bcl-2-myc transgenic mice have lymphomyeloid differentiation potential and reveal developmental differences in cell survival. EMBO J 1996; 15: 3823\u20133834.","journal-title":"EMBO J"},{"key":"BFcddis201643_CR45","doi-asserted-by":"publisher","first-page":"13789","DOI":"10.1073\/pnas.0605944103","volume":"103","author":"E Hobeika","year":"2006","unstructured":"Hobeika E, Thiemann S, Storch B, Jumaa H, Nielsen PJ, Pelanda R et al. Testing gene function early in the B cell lineage in mb1-cre mice. Proc Natl Acad Sci USA 2006; 103: 13789\u201313794.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis201643_CR46","doi-asserted-by":"publisher","first-page":"9003","DOI":"10.1128\/MCB.23.24.9003-9013.2003","volume":"23","author":"MP McCormack","year":"2003","unstructured":"McCormack MP, Forster A, Drynan L, Pannell R, Rabbitts TH . The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development. Mol Cell Biol 2003; 23: 9003\u20139013.","journal-title":"Mol Cell Biol"},{"key":"BFcddis201643_CR47","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S1074-7613(02)00366-7","volume":"17","author":"H Igarashi","year":"2002","unstructured":"Igarashi H, Gregory SC, Yokota T, Sakaguchi N, Kincade PW . Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 2002; 17: 117\u2013130.","journal-title":"Immunity"},{"key":"BFcddis201643_CR48","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1126\/science.281.5381.1322","volume":"281","author":"JM Adams","year":"1998","unstructured":"Adams JM, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science 1998; 281: 1322\u20131326.","journal-title":"Science"},{"key":"BFcddis201643_CR49","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/ni0707-665","volume":"8","author":"M Schmidt-Supprian","year":"2007","unstructured":"Schmidt-Supprian M, Rajewsky K . Vagaries of conditional gene targeting. Nat Immunol 2007; 8: 665\u2013668.","journal-title":"Nat Immunol"},{"key":"BFcddis201643_CR50","doi-asserted-by":"publisher","first-page":"e1590","DOI":"10.1038\/cddis.2014.561","volume":"6","author":"JD Leverson","year":"2015","unstructured":"Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC, Xue J et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis 2015; 6: e1590.","journal-title":"Cell Death Dis"},{"key":"BFcddis201643_CR51","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1038\/cdd.2015.73","volume":"22","author":"CM Goodwin","year":"2015","unstructured":"Goodwin CM, Rossanese OW, Olejniczak ET, Fesik SW . Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer. Cell Death Differ 2015; 22: 2098\u20132106.","journal-title":"Cell Death Differ"},{"key":"BFcddis201643_CR52","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/318533a0","volume":"318","author":"JM Adams","year":"1985","unstructured":"Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S et al. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 1985; 318: 533\u2013538.","journal-title":"Nature"},{"key":"BFcddis201643_CR53","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1073\/pnas.1321259110","volume":"111","author":"T Okamoto","year":"2014","unstructured":"Okamoto T, Coultas L, Metcalf D, van Delft MF, Glaser SP, Takiguchi M et al. Enhanced stability of Mcl1, a prosurvival Bcl2 relative, blunts stress-induced apoptosis, causes male sterility, and promotes tumorigenesis. Proc Natl Acad Sci USA 2014; 111: 261\u2013266.","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis201643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis201643","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis201643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T09:05:35Z","timestamp":1672823135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis201643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,10]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["BFcddis201643"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.43","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,10]]},"assertion":[{"value":"2 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"SG, ARDD, GLK, PB, JMA and AS are employed by The Walter and Eliza Hall Institute, which receives milestone payments from Genentech and AbbVie for the development of ABT-199 for cancer therapy.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}