{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:14:18Z","timestamp":1789683258373,"version":"4.0.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,1,10]],"date-time":"2014-01-10T00:00:00Z","timestamp":1389312000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer Journal"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapeutic options are limited for elderly patients with acute myeloid leukemia (AML). A phase Ib\/II study was undertaken to evaluate the maximum-tolerated dose (MTD) and preliminary efficacy of the pan-histone deacetylase inhibitor panobinostat (LBH589) in combination with azacitidine in patients with AML or high-risk myelodysplastic syndrome (MDS) na\u00efve to intensive chemotherapy. Thirty-nine patients (AML=29, MDS=10) received azacitidine 75\u2009mg\/m<jats:sup>2<\/jats:sup> subcutaneously (days 1\u20135) and oral panobinostat (starting on day 5, thrice weekly for seven doses) in 28-day cycles until toxicity or disease progression. Dose-limiting toxicities during the phase Ib stage were observed in 0\/4 patients receiving 10\u2009mg panobinostat, in 1\/7 patients (fatigue) receiving 20\u2009mg, in 1\/6 patients (fatigue) receiving 30\u2009mg and in 4\/5 patients (fatigue, syncope, hyponatremia and somnolence) receiving 40\u2009mg. In phase II, an additional 17 patients received panobinostat at a MTD of 30\u2009mg. The overall response rate (ORR=CR+CRi+PR) in patients with AML was 31% (9\/29) and that in patients with MDS was 50% (5\/10). After a median follow-up of 13 months, the median overall survival was 8 and 16 months in patients with AML and MDS, respectively. Increased histone H3 and H4 acetylation was a useful early biomarker of clinical response. Combining panobinostat with azacitidine was tolerable and clinically active in high-risk MDS\/AML patients, warranting further exploration.<\/jats:p>","DOI":"10.1038\/bcj.2013.68","type":"journal-article","created":{"date-parts":[[2014,1,10]],"date-time":"2014-01-10T14:23:10Z","timestamp":1389363790000},"page":"e170-e170","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome"],"prefix":"10.1038","volume":"4","author":[{"given":"P","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Mithraprabhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Cummings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H B","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Perugini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Avery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Patil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Mollee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Grigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"D'Andrea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Dear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,1,10]]},"reference":[{"key":"BFbcj201368_CR1","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/cncr.22496","volume":"109","author":"A Burnett","year":"2007","unstructured":"Burnett A, Milligan D, Prentice A, Goldstone A, Mcmullin M, Hills R et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007; 109: 1114\u20131124.","journal-title":"Cancer"},{"key":"BFbcj201368_CR2","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1200\/JCO.2002.04.117","volume":"20","author":"LR Silverman","year":"2002","unstructured":"Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R et al. Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B. J Clin Oncol 2002; 20: 2429.","journal-title":"J Clin Oncol"},{"key":"BFbcj201368_CR3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S1470-2045(09)70003-8","volume":"10","author":"P Fenaux","year":"2009","unstructured":"Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009; 10: 223\u2013232.","journal-title":"Lancet Oncol"},{"key":"BFbcj201368_CR4","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1200\/JCO.2011.38.9429","volume":"30","author":"HM Kantarjian","year":"2012","unstructured":"Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30: 2670\u20132677.","journal-title":"J Clin Oncol"},{"key":"BFbcj201368_CR5","first-page":"843","volume":"114","author":"S Thepot","year":"2009","unstructured":"Thepot S, Itzykson R, Seegers V, Recher C, Quesnel B, Delaunay J et al. Azacytidine (AZA) as First Line Therapy in AML: Results of the French ATU Program. ASH Annual Meeting Abstracts 2009; 114: 843.","journal-title":"ASH Annual Meeting Abstracts"},{"key":"BFbcj201368_CR6","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1002\/cncr.26354","volume":"118","author":"L Maurillo","year":"2012","unstructured":"Maurillo L, Venditti A, Spagnoli A, Gaidano G, Ferrero D, Oliva E et al. Azacitidine for the treatment of patients with acute myeloid leukemia. Cancer 2012; 118: 1014\u20131022.","journal-title":"Cancer"},{"key":"BFbcj201368_CR7","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1182\/blood-2011-06-358705","volume":"119","author":"S Agrawal-Singh","year":"2012","unstructured":"Agrawal-Singh S, Isken F, Agelopoulos K, Klein H-U, Thoennissen NH, Koehler G et al. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene. Blood 2012; 119: 2346\u20132357.","journal-title":"Blood"},{"key":"BFbcj201368_CR8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/sj.leu.2404050","volume":"20","author":"P Maslak","year":"2005","unstructured":"Maslak P, Chanel S, Camacho L, Soignet S, Pandolfi P, Guernah I et al. Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia 2005; 20: 212\u2013217.","journal-title":"Leukemia"},{"key":"BFbcj201368_CR9","doi-asserted-by":"publisher","first-page":"6361","DOI":"10.1158\/0008-5472.CAN-06-0080","volume":"66","author":"S Gore","year":"2006","unstructured":"Gore S, Baylin S, Sugar E, Carraway H, Miller C, Carducci M et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66: 6361.","journal-title":"Cancer Res"},{"key":"BFbcj201368_CR10","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1182\/blood-2009-02-203547","volume":"114","author":"TE Fandy","year":"2009","unstructured":"Fandy TE, Herman JG, Kerns P, Jiemjit A, Sugar EA, Choi S-H et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood 2009; 114: 2764\u20132773.","journal-title":"Blood"},{"key":"BFbcj201368_CR11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.18632\/oncotarget.106","volume":"1","author":"E Raffoux","year":"2010","unstructured":"Raffoux E, Cras A, Recher C, Bo\u00eblle P-Y, de Labarthe A, Turlure P et al. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Oncotarget 2010; 1: 34.","journal-title":"Oncotarget"},{"key":"BFbcj201368_CR12","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1182\/blood-2007-03-078576","volume":"110","author":"AO Soriano","year":"2007","unstructured":"Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F et al. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 2007; 110: 2302\u20132308.","journal-title":"Blood"},{"key":"BFbcj201368_CR13","first-page":"608","volume":"118","author":"G Garcia-Manero","year":"2011","unstructured":"Garcia-Manero G, Estey EH, Jabbour E, Borthakur G, Kadia T, Naqvi K et al. Final Report of a Phase II Study of 5-Azacitidine and Vorinostat in Patients (pts) with Newly Diagnosed Myelodysplastic Syndrome (MDS) or Acute Myelogenous Leukemia (AML) Not Eligible for Clinical Trials Because Poor Performance and Presence of Other Comorbidities. ASH Annual Meeting Abstracts 2011; 118: 608.","journal-title":"ASH Annual Meeting Abstracts"},{"issue":"15_suppl","key":"BFbcj201368_CR14","first-page":"6521","volume":"29","author":"O Odenike","year":"2011","unstructured":"Odenike O, Godley LA, Madzo J, Karrison T, Green M, Artz AS et al. A phase I and pharmacodynamic (PD) study of the histone deacetylase (HDAC) inhibitor belinostat (BEL) plus azacitidine (AZC) in advanced myeloid malignancies. ASCO Meeting Abstracts 2011; 29 (15_suppl): 6521.","journal-title":"ASCO Meeting Abstracts"},{"key":"BFbcj201368_CR15","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/5047","volume":"21","author":"EE Cameron","year":"1999","unstructured":"Cameron EE, Bachman KE, My\u00f6h\u00e4nen S, Herman JG, Baylin SB . Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999; 21: 103\u2013107.","journal-title":"Nat Genet"},{"key":"BFbcj201368_CR16","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1038\/leu.2013.38","volume":"27","author":"D DeAngelo","year":"2013","unstructured":"DeAngelo D, Spencer A, Bhalla K, Prince H, Fischer T, Kindler T et al. Phase Ia\/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia 2013; 27: 1628\u20131636.","journal-title":"Leukemia"},{"key":"BFbcj201368_CR17","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1200\/JCO.2008.17.1058","volume":"27","author":"RM Lyons","year":"2009","unstructured":"Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 2009; 27: 1850\u20131856.","journal-title":"J Clin Oncol"},{"key":"BFbcj201368_CR18","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1002\/ajh.21482","volume":"84","author":"MG Martin","year":"2009","unstructured":"Martin MG, Walgren RA, Procknow E, Uy GL, Stockerl Goldstein K, Cashen AF et al. A phase II study of 5 day intravenous azacitidine in patients with myelodysplastic syndromes. Am J Hematol 2009; 84: 560\u2013564.","journal-title":"Am J Hematol"},{"key":"BFbcj201368_CR19","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1200\/JCO.2003.04.036","volume":"21","author":"BD Cheson","year":"2003","unstructured":"Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642.","journal-title":"J Clin Oncol"},{"key":"BFbcj201368_CR20","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1182\/blood-2005-10-4149","volume":"108","author":"BD Cheson","year":"2006","unstructured":"Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006; 108: 419\u2013425.","journal-title":"Blood"},{"key":"BFbcj201368_CR21","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1182\/blood-2009-03-209262","volume":"114","author":"JW Vardiman","year":"2009","unstructured":"Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937\u2013951.","journal-title":"Blood"},{"key":"BFbcj201368_CR22","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1182\/blood-2009-11-254441","volume":"116","author":"D Grimwade","year":"2010","unstructured":"Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116: 354\u2013365.","journal-title":"Blood"},{"key":"BFbcj201368_CR23","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1182\/blood.V89.6.2079","volume":"89","author":"P Greenberg","year":"1997","unstructured":"Greenberg P, Cox C, Le Beau M . International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes. Blood 1997; 89: 2079\u20132088.","journal-title":"Blood"},{"key":"BFbcj201368_CR24","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/ejh.12079","volume":"90","author":"MT Voso","year":"2013","unstructured":"Voso MT, Breccia M, Lunghi M, Poloni A, Niscola P, Finelli C et al. Rapid loss of response after withdrawal of treatment with azacitidine: a case series in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Eur J Haematol 2013; 90: 345\u2013348.","journal-title":"Eur J Haematol"},{"key":"BFbcj201368_CR25","doi-asserted-by":"publisher","first-page":"875","DOI":"10.4161\/epi.20983","volume":"7","author":"L Rigby","year":"2012","unstructured":"Rigby L, Muscat A, Ashley D, Algar E . Methods for the analysis of histone H3 and H4 acetylation in blood. Epigenetics 2012; 7: 875\u2013882.","journal-title":"Epigenetics"},{"key":"BFbcj201368_CR26","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1111\/bjh.12388","volume":"162","author":"S Mithraprabhu","year":"2013","unstructured":"Mithraprabhu S, Khong T, Jones SS, Spencer A . Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol 2013; 162: 559\u2013562.","journal-title":"Br J Haematol"},{"key":"BFbcj201368_CR27","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1038\/leu.2012.346","volume":"27","author":"M Perugini","year":"2012","unstructured":"Perugini M, Iarossi D, Kok C, Cummings N, Diakiw S, Brown A et al. GADD45A methylation predicts poor overall survival in acute myeloid leukemia and is associated with IDH1\/2 and DNMT3A mutations. Leukemia 2012; 27: 1588\u20131592.","journal-title":"Leukemia"},{"key":"BFbcj201368_CR28","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1172\/JCI111731","volume":"75","author":"R Humphries","year":"1985","unstructured":"Humphries R, Dover G, Young NS, Moore JG, Charache S, Ley T et al. 5-Azacytidine acts directly on both erythroid precursors and progenitors to increase production of fetal hemoglobin. J Clin Invest 1985; 75: 547.","journal-title":"J Clin Invest"},{"key":"BFbcj201368_CR29","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/nm1579","volume":"13","author":"SE Mullican","year":"2007","unstructured":"Mullican SE, Zhang S, Konopleva M, Ruvolo V, Andreeff M, Milbrandt J et al. Abrogation of nuclear receptors Nr4a3 andNr4a1 leads to development of acute myeloid leukemia. Nat Med 2007; 13: 730\u2013735.","journal-title":"Nat Med"},{"key":"BFbcj201368_CR30","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1038\/leu.2012.366","volume":"27","author":"L Zhou","year":"2012","unstructured":"Zhou L, Ruvolo V, McQueen T, Chen W, Samudio I, Conneely O et al. HDAC inhibition by SNDX-275 (Entinostat) restores expression of silenced leukemia-associated transcription factors Nur77 and Nor1 and of key pro-apoptotic proteins in AML. Leukemia 2012; 27: 1358\u20131368.","journal-title":"Leukemia"},{"key":"BFbcj201368_CR31","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/jnci\/85.5.365","volume":"85","author":"NK Aaronson","year":"1993","unstructured":"Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365\u2013376.","journal-title":"J Natl Cancer Inst"},{"key":"BFbcj201368_CR32","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3324\/haematol.2012.067892","volume":"98","author":"B Deschler","year":"2013","unstructured":"Deschler B, Ihorst G, Platzbecker U, Germing U, Marz E, de Figuerido M et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica 2013; 98: 208\u2013216.","journal-title":"Haematologica"},{"key":"BFbcj201368_CR33","first-page":"604","volume":"116","author":"G Garcia-Manero","year":"2010","unstructured":"Garcia-Manero G, Estey EH, Jabbour E, Kadia T, Estrov Z, Cortes J et al. Phase II Study of 5-Azacitidine and Vorinostat In Patients (pts) with Newly Diagnosed Myelodysplastic Syndrome (MDS) or Acute Myelogenous Leukemia (AML) Not Eligible for Clinical Trials Because Poor Performance or Presence of Other comorbidities. ASH Annual Meeting Abstracts 2010; 116: 604.","journal-title":"ASH Annual Meeting Abstracts"},{"key":"BFbcj201368_CR34","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1182\/blood-2007-06-098061","volume":"111","author":"G Garcia-Manero","year":"2008","unstructured":"Garcia-Manero G, Yang H, Bueso-Ramos C, Ferrajoli A, Cortes J, Wierda WG et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood 2008; 111: 1060\u20131066.","journal-title":"Blood"},{"key":"BFbcj201368_CR35","doi-asserted-by":"publisher","first-page":"6361","DOI":"10.1158\/0008-5472.CAN-06-0080","volume":"66","author":"SD Gore","year":"2006","unstructured":"Gore SD, Baylin S, Sugar E, Carraway H, Miller CB, Carducci M et al. Combined DNA Methyltransferase and Histone Deacetylase Inhibition in the Treatment of Myeloid Neoplasms. Cancer Res 2006; 66: 6361.","journal-title":"Cancer Res"},{"key":"BFbcj201368_CR36","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/jnci\/85.5.365","volume":"85","author":"NK Aaronson","year":"1993","unstructured":"Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365\u2013376.","journal-title":"J Natl Cancer Inst"},{"key":"BFbcj201368_CR37","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3324\/haematol.2012.067892","volume":"98","author":"B Deschler","year":"2013","unstructured":"Deschler B, Ihorst G, Platzbecker U, Germing U, M\u00e4rz E, de Figuerido M et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica 2013; 98: 208\u2013216.","journal-title":"Haematologica"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/bcj201368.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/bcj201368","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/bcj201368.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T22:55:36Z","timestamp":1672959336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/bcj201368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,10]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1]]}},"alternative-id":["BFbcj201368"],"URL":"https:\/\/doi.org\/10.1038\/bcj.2013.68","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,10]]},"assertion":[{"value":"4 September 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2013","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2013","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AS and AW received research funding from Novartis and Celgene.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}