{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:05:14Z","timestamp":1782911114161,"version":"3.54.5"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:00:00Z","timestamp":1509667200000},"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":["Leukemia"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1038\/leu.2017.321","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T14:43:51Z","timestamp":1509720231000},"page":"920-930","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy"],"prefix":"10.1038","volume":"32","author":[{"given":"V K","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Lamothe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M L","family":"Ayres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Balakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-0168","authenticated-orcid":false,"given":"C","family":"Ivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Morse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Keating","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W G","family":"Wierda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Marszalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Gandhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,3]]},"reference":[{"key":"BFleu2017321_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nrc3702","volume":"14","author":"RW Hendriks","year":"2014","unstructured":"Hendriks RW, Yuvaraj S, Kil LP . Targeting Bruton's tyrosine kinase in B cell malignancies. Nat Rev Cancer 2014; 14: 219\u2013232.","journal-title":"Nat Rev Cancer"},{"key":"BFleu2017321_CR2","doi-asserted-by":"publisher","first-page":"4389","DOI":"10.1182\/blood-2003-12-4312","volume":"103","author":"FK Stevenson","year":"2004","unstructured":"Stevenson FK, Caligaris-Cappio F . Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood 2004; 103: 4389\u20134395.","journal-title":"Blood"},{"key":"BFleu2017321_CR3","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1200\/JCO.2013.53.1046","volume":"32","author":"S Ponader","year":"2014","unstructured":"Ponader S, Burger JA . Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies. J Clin Oncol 2014; 32: 1830\u20131839.","journal-title":"J Clin Oncol"},{"key":"BFleu2017321_CR4","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.1182\/blood-2012-05-423194","volume":"120","author":"A Wiestner","year":"2012","unstructured":"Wiestner A . Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia. Blood 2012; 120: 4684\u20134691.","journal-title":"Blood"},{"key":"BFleu2017321_CR5","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1056\/NEJMoa1509981","volume":"374","author":"JC Byrd","year":"2016","unstructured":"Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med 2016; 374: 323\u2013332.","journal-title":"N Engl J Med"},{"key":"BFleu2017321_CR6","doi-asserted-by":"publisher","first-page":"13075","DOI":"10.1073\/pnas.1004594107","volume":"107","author":"LA Honigberg","year":"2010","unstructured":"Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA 2010; 107: 13075\u201313080.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2017321_CR7","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.1182\/blood-2011-01-328484","volume":"117","author":"SE Herman","year":"2011","unstructured":"Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 2011; 117: 6287\u20136296.","journal-title":"Blood"},{"key":"BFleu2017321_CR8","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1158\/1078-0432.CCR-16-1446","volume":"23","author":"V Patel","year":"2017","unstructured":"Patel V, Balakrishnan K, Bibikova E, Ayres M, Keating MJ, Wierda WG et al. Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells. Clin Cancer Res 2017; 23: 3734\u20133743.","journal-title":"Clin Cancer Res"},{"key":"BFleu2017321_CR9","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1182\/blood-2013-06-507947","volume":"122","author":"JA Dubovsky","year":"2013","unstructured":"Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood 2013; 122: 2539\u20132549.","journal-title":"Blood"},{"key":"BFleu2017321_CR10","doi-asserted-by":"publisher","first-page":"dju204","DOI":"10.1093\/jnci\/dju204","volume":"106","author":"W Gao","year":"2014","unstructured":"Gao W, Wang M, Wang L, Lu H, Wu S, Dai B et al. Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells. J Natl Cancer Inst 2014; 106: dju204.","journal-title":"J Natl Cancer Inst"},{"key":"BFleu2017321_CR11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1056\/NEJMoa1400376","volume":"371","author":"JC Byrd","year":"2014","unstructured":"Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371: 213\u2013223.","journal-title":"N Engl J Med"},{"key":"BFleu2017321_CR12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/S1470-2045(13)70513-8","volume":"15","author":"S O'Brien","year":"2014","unstructured":"O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b\/2 trial. Lancet Oncol 2014; 15: 48\u201358.","journal-title":"Lancet Oncol"},{"key":"BFleu2017321_CR13","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/S1470-2045(16)30212-1","volume":"17","author":"S O'Brien","year":"2016","unstructured":"O'Brien S, Jones JA, Coutre SE, Mato AR, Hillmen P, Tam C et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol 2016; 17: 1409\u20131418.","journal-title":"Lancet Oncol"},{"key":"BFleu2017321_CR14","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","volume":"373","author":"JA Burger","year":"2015","unstructured":"Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med 2015; 373: 2425\u20132437.","journal-title":"N Engl J Med"},{"key":"BFleu2017321_CR15","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1182\/blood.V94.11.3658","volume":"94","author":"JA Burger","year":"1999","unstructured":"Burger JA, Burger M, Kipps TJ . Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 1999; 94: 3658\u20133667.","journal-title":"Blood"},{"key":"BFleu2017321_CR16","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1038\/leu.2015.105","volume":"29","author":"K Balakrishnan","year":"2015","unstructured":"Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG et al. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K\/AKT\/S6 pathway and promotes apoptosis in CLL. Leukemia 2015; 29: 1811\u20131822.","journal-title":"Leukemia"},{"key":"BFleu2017321_CR17","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1182\/blood-2008-07-170415","volume":"113","author":"JA Burger","year":"2009","unstructured":"Burger JA, Quiroga MP, Hartmann E, Burkle A, Wierda WG, Keating MJ et al. High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation. Blood 2009; 113: 3050\u20133058.","journal-title":"Blood"},{"key":"BFleu2017321_CR18","doi-asserted-by":"publisher","first-page":"E1500","DOI":"10.1073\/pnas.1300616110","volume":"110","author":"SS Chen","year":"2013","unstructured":"Chen SS, Batliwalla F, Holodick NE, Yan XJ, Yancopoulos S, Croce CM et al. Autoantigen can promote progression to a more aggressive TCL1 leukemia by selecting variants with enhanced B-cell receptor signaling. Proc Natl Acad Sci USA 2013; 110: E1500\u2013E1507.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2017321_CR19","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1158\/1078-0432.CCR-15-0781","volume":"21","author":"SE Herman","year":"2015","unstructured":"Herman SE, Mustafa RZ, Jones J, Wong DH, Farooqui M, Wiestner A . Treatment with ibrutinib inhibits BTK- and VLA-4-dependent adhesion of chronic lymphocytic leukemia cells in vivo. Clin Cancer Res 2015; 21: 4642\u20134651.","journal-title":"Clin Cancer Res"},{"key":"BFleu2017321_CR20","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1182\/blood-2011-10-386417","volume":"119","author":"S Ponader","year":"2012","unstructured":"Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 2012; 119: 1182\u20131189.","journal-title":"Blood"},{"key":"BFleu2017321_CR21","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1158\/1078-0432.CCR-15-1965","volume":"22","author":"CU Niemann","year":"2016","unstructured":"Niemann CU, Herman SE, Maric I, Gomez-Rodriguez J, Biancotto A, Chang BY et al. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib\u2014findings from an investigator-initiated phase II study. Clin Cancer Res 2016; 22: 1572\u20131582.","journal-title":"Clin Cancer Res"},{"key":"BFleu2017321_CR22","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1182\/blood-2014-01-547869","volume":"123","author":"HE Kohrt","year":"2014","unstructured":"Kohrt HE, Sagiv-Barfi I, Rafiq S, Herman SE, Butchar JP, Cheney C et al. Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood 2014; 123: 1957\u20131960.","journal-title":"Blood"},{"key":"BFleu2017321_CR23","doi-asserted-by":"publisher","first-page":"65968","DOI":"10.18632\/oncotarget.11782","volume":"7","author":"S Fiorcari","year":"2016","unstructured":"Fiorcari S, Maffei R, Audrito V, Martinelli S, Ten Hacken E, Zucchini P et al. Ibrutinib modifies the function of monocyte\/macrophage population in chronic lymphocytic leukemia. Oncotarget 2016; 7: 65968\u201365981.","journal-title":"Oncotarget"},{"key":"BFleu2017321_CR24","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1074\/jbc.M115.687251","volume":"291","author":"L Ren","year":"2016","unstructured":"Ren L, Campbell A, Fang H, Gautam S, Elavazhagan S, Fatehchand K et al. Analysis of the effects of the Bruton's tyrosine kinase (Btk) inhibitor ibrutinib on monocyte Fcgamma receptor (FcgammaR) function. J Biol Chem 2016; 291: 3043\u20133052.","journal-title":"J Biol Chem"},{"key":"BFleu2017321_CR25","doi-asserted-by":"publisher","first-page":"15524","DOI":"10.1073\/pnas.242606799","volume":"99","author":"GA Calin","year":"2002","unstructured":"Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524\u201315529.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2017321_CR26","doi-asserted-by":"publisher","first-page":"13944","DOI":"10.1073\/pnas.0506654102","volume":"102","author":"A Cimmino","year":"2005","unstructured":"Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102: 13944\u201313949.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2017321_CR27","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1182\/blood.V91.9.3379","volume":"91","author":"S Kitada","year":"1998","unstructured":"Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood 1998; 91: 3379\u20133389.","journal-title":"Blood"},{"key":"BFleu2017321_CR28","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.neo.2014.10.002","volume":"16","author":"K Balakrishnan","year":"2014","unstructured":"Balakrishnan K, Burger JA, Fu M, Doifode T, Wierda WG, Gandhi V . Regulation of Mcl-1 expression in context to bone marrow stromal microenvironment in chronic lymphocytic leukemia. Neoplasia 2014; 16: 1036\u20131046.","journal-title":"Neoplasia"},{"key":"BFleu2017321_CR29","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1038\/leu.2017.11","volume":"31","author":"TM Herndon","year":"2017","unstructured":"Herndon TM, Chen SS, Saba NS, Valdez J, Emson C, Gatmaitan M et al. Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood. Leukemia 2017; 31: 1340\u20131347.","journal-title":"Leukemia"},{"key":"BFleu2017321_CR30","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/nature03579","volume":"435","author":"T Oltersdorf","year":"2005","unstructured":"Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005; 435: 677\u2013681.","journal-title":"Nature"},{"key":"BFleu2017321_CR31","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nm.3048","volume":"19","author":"AJ Souers","year":"2013","unstructured":"Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013; 19: 202\u2013208.","journal-title":"Nat Med"},{"key":"BFleu2017321_CR32","doi-asserted-by":"publisher","first-page":"5814","DOI":"10.1158\/1078-0432.CCR-17-0650","volume":"23","author":"CU Niemann","year":"2017","unstructured":"Niemann CU, Mora-Jensen HI, Dadashian EL, Krantz F, Covey T, Chen SS et al. Combined BTK and PI3Kdelta inhibition with acalabrutinib and ACP-319 improves survival and tumor control in CLL mouse model. Clin Cancer Res 2017; 23: 5814\u20135823.","journal-title":"Clin Cancer Res"},{"key":"BFleu2017321_CR33","doi-asserted-by":"publisher","first-page":"3705","DOI":"10.1158\/1078-0432.CCR-14-2809","volume":"21","author":"F Cervantes-Gomez","year":"2015","unstructured":"Cervantes-Gomez F, Lamothe B, Woyach JA, Wierda WG, Keating MJ, Balakrishnan K et al. Pharmacological and protein profiling suggests venetoclax (ABT-199) as optimal partner with ibrutinib in chronic lymphocytic leukemia. Clin Cancer Res 2015; 21: 3705\u20133715.","journal-title":"Clin Cancer Res"},{"key":"BFleu2017321_CR34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00025","volume":"1","author":"Q Yang","year":"2017","unstructured":"Yang Q, Shah P, Korkut A, Fernandes SM, Hanna J, Brown JR et al. Changes in Bcl-2 family protein profile during idelalisib therapy mimic those during duvelisib therapy in CLL lymphocytes. JCO Precis Oncol 2017; 1: 1\u20135.","journal-title":"JCO Precis Oncol"},{"key":"BFleu2017321_CR35","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1038\/leu.2016.382","volume":"31","author":"VM Patel","year":"2017","unstructured":"Patel VM, Balakrishnan K, Douglas M, Tibbitts T, Xu EY, Kutok JL et al. Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199). Leukemia 2017; 31: 1872\u20131881.","journal-title":"Leukemia"},{"key":"BFleu2017321_CR36","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1038\/leu.2017.32","volume":"31","author":"J Deng","year":"2017","unstructured":"Deng J, Isik E, Fernandes SM, Brown JR, Letai A, Davids MS . Bruton's tyrosine kinase inhibition increases BCL-2 dependence and enhances sensitivity to venetoclax in chronic lymphocytic leukemia. Leukemia 2017; 31: 2075\u20132208.","journal-title":"Leukemia"},{"key":"BFleu2017321_CR37","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.molcel.2006.02.009","volume":"21","author":"U Maurer","year":"2006","unstructured":"Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR . Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 2006; 21: 749\u2013760.","journal-title":"Mol Cell"},{"key":"BFleu2017321_CR38","doi-asserted-by":"publisher","first-page":"4032","DOI":"10.4161\/cc.8.24.10111","volume":"8","author":"C Xu","year":"2009","unstructured":"Xu C, Kim NG, Gumbiner BM . Regulation of protein stability by GSK3 mediated phosphorylation. Cell Cycle 2009; 8: 4032\u20134039.","journal-title":"Cell Cycle"},{"key":"BFleu2017321_CR39","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ccr.2007.12.002","volume":"13","author":"T Kang","year":"2008","unstructured":"Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung MC et al. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell 2008; 13: 36\u201347.","journal-title":"Cancer Cell"},{"key":"BFleu2017321_CR40","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1038\/leu.2015.46","volume":"29","author":"H Bhanot","year":"2015","unstructured":"Bhanot H, Reddy MM, Nonami A, Weisberg EL, Bonal D, Kirschmeier PT et al. Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells. Leukemia 2015; 29: 1555\u20131563.","journal-title":"Leukemia"},{"key":"BFleu2017321_CR41","doi-asserted-by":"publisher","first-page":"7410","DOI":"10.1038\/sj.onc.1209086","volume":"24","author":"EL Greer","year":"2005","unstructured":"Greer EL, Brunet A . FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 2005; 24: 7410\u20137425.","journal-title":"Oncogene"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/leu2017321.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/leu2017321","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/leu.2017.321","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/leu2017321.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T08:03:27Z","timestamp":1719561807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/leu2017321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,3]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["BFleu2017321"],"URL":"https:\/\/doi.org\/10.1038\/leu.2017.321","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,3]]},"assertion":[{"value":"30 July 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"VG and WGW received research and clinical trial funding from Acerta. JPC is an employee of Acerta. The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}