{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T08:37:54Z","timestamp":1770539874772,"version":"3.49.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":1315,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81270645"],"award-info":[{"award-number":["81270645"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008868","name":"Science and Technology Department of Jiangsu Province","doi-asserted-by":"crossref","award":["BE2017655"],"award-info":[{"award-number":["BE2017655"]}],"id":[{"id":"10.13039\/501100008868","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jiangsu Provincial Medical Talent","award":["ZDRCA2016045"],"award-info":[{"award-number":["ZDRCA2016045"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA016672"],"award-info":[{"award-number":["CA016672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","exphem.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Hematology"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1016\/j.exphem.2018.08.002","type":"journal-article","created":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T12:25:38Z","timestamp":1533903938000},"page":"49-59.e1","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Epigenetic modification enhances the cytotoxicity of busulfan and4-hydroperoxycyclophosphamide in AML cells"],"prefix":"10.1016","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-8247","authenticated-orcid":false,"given":"Benigno C.","family":"Valdez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uday","family":"Popat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-5037","authenticated-orcid":false,"given":"Richard E.","family":"Champlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borje S.","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.exphem.2018.08.002_bib0001","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.bbmt.2008.12.489","article-title":"Busulfan in hematopoietic stem cell transplantation","volume":"15","author":"Ciurea","year":"2009","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0002","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1056\/NEJM198312013092202","article-title":"Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide","volume":"309","author":"Santos","year":"1983","journal-title":"N Engl J Med"},{"key":"10.1016\/j.exphem.2018.08.002_bib0003","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1038\/sj.bmt.1702351","article-title":"Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy)","volume":"25","author":"Andersson","year":"2000","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0004","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/bbmt.2002.v8.pm11939604","article-title":"Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study","volume":"8","author":"Andersson","year":"2002","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0005","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1182\/blood-2013-08-519009","article-title":"Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation","volume":"122","author":"Bredeson","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0006","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1182\/blood-2013-07-514448","article-title":"Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI","volume":"122","author":"Copelan","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0007","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/bmt.2015.238","article-title":"Busulfan fludarabine vs busulfan cyclophosphamide as a preparative regimen before allogeneic hematopoietic cell transplantation: systematic review and meta-analysis","volume":"51","author":"Ben-Barouch","year":"2016","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0008","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1200\/JCO.2013.48.8114","volume":"31","author":"Nagler","year":"2013","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.exphem.2018.08.002_bib0009","doi-asserted-by":"crossref","unstructured":"Cornelissen JJ, van Putten WL, Verdonck LF, et al. Results of a HOVON\/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109:3658\u20133666.","DOI":"10.1182\/blood-2006-06-025627"},{"key":"10.1016\/j.exphem.2018.08.002_bib0010","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1053\/bbmt.2002.v8.pm12374451","article-title":"Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes","volume":"8","author":"Russell","year":"2002","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0011","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1182\/blood-2004-02-0414","article-title":"Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS","volume":"104","author":"de Lima","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0012","doi-asserted-by":"crossref","unstructured":"Andersson BS, Valdez BC. Pretransplant conditioning with fludarabine and IV busulfan, reduced toxicity and increased safety without compromising antitumor efficacy and overall treatment effect? Bone Marrow Transplant. 2016;51:919\u2013920.","DOI":"10.1038\/bmt.2016.110"},{"key":"10.1016\/j.exphem.2018.08.002_bib0013","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bbmt.2016.11.001","article-title":"Clofarabine plus busulfan is an effective conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia: Long-term study results","volume":"23","author":"Kebriaei","year":"2017","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0014","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/bmt.2016.322","article-title":"Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML\/MDS patients","volume":"52","author":"Andersson","year":"2017","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0015","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1756-8722-6-15","volume":"6","author":"Liu","year":"2013","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.exphem.2018.08.002_bib0016","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/S1470-2045(15)00200-4","article-title":"Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial","volume":"16","author":"Rambaldi","year":"2015","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.exphem.2018.08.002_bib0017","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0163-7258(85)90053-1","article-title":"Molecular, cellular and animal pharmacology of 5-aza-2\u2032-deoxycytidine","volume":"30","author":"Momparler","year":"1985","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.exphem.2018.08.002_bib0018","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.leukres.2009.08.014","article-title":"5-Aza-2\u2032-deoxycytidine sensitizes busulfan-resistant myeloid leukemia cells by regulating expression of genes involved in cell cycle checkpoint and apoptosis","volume":"34","author":"Valdez","year":"2010","journal-title":"Leuk Res"},{"key":"10.1016\/j.exphem.2018.08.002_bib0019","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1182\/blood-2010-11-320093","article-title":"Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML","volume":"118","author":"Scandura","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0020","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13148-017-0411-x","article-title":"A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML","volume":"9","author":"Gore","year":"2017","journal-title":"Clin Epigenetics"},{"key":"10.1016\/j.exphem.2018.08.002_bib0021","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0022-3565(25)28610-4","article-title":"Enzymatic basis of cyclophosphamide activation by hepatic microsomes of the rat","volume":"174","author":"Cohen","year":"1970","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.exphem.2018.08.002_bib0022","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1182\/blood-2002-06-1860","article-title":"Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation","volume":"101","author":"McDonald","year":"2003","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0023","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2165\/00003088-200038040-00001","article-title":"Metabolism and pharmacokinetics of oxazaphosphorines","volume":"38","author":"Boddy","year":"2000","journal-title":"Clin Pharmacokinet"},{"key":"10.1016\/j.exphem.2018.08.002_bib0024","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/j.leukres.2008.01.016","article-title":"Altered gene expression in busulfan-resistant human myeloid leukemia","volume":"32","author":"Valdez","year":"2008","journal-title":"Leuk Res"},{"key":"10.1016\/j.exphem.2018.08.002_bib0025","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/leu.2008.158","article-title":"The dual PI3 kinase\/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML","volume":"2","author":"Kojima","year":"2008","journal-title":"Leukemia"},{"key":"10.1016\/j.exphem.2018.08.002_bib0026","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"10.1016\/j.exphem.2018.08.002_bib0027","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.182.5.1545","article-title":"Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl","volume":"182","author":"Martin","year":"1995","journal-title":"J Exp Med"},{"key":"10.1016\/j.exphem.2018.08.002_bib0028","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv Enzyme Regul"},{"key":"10.1016\/j.exphem.2018.08.002_bib0029","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.exphem.2015.02.001","article-title":"Comparison of the cytotoxicity of cladribine and clofarabine when combined with fludarabine and busulfan in AML cells: Enhancement of cytotoxicity with epigenetic modulators","volume":"43","author":"Valdez","year":"2015","journal-title":"Exp Hematol"},{"key":"10.1016\/j.exphem.2018.08.002_bib0030","doi-asserted-by":"crossref","first-page":"3908","DOI":"10.18632\/oncotarget.23386","article-title":"Combination of a hypomethylating agent and inhibitors of PARP and HDAC traps PARP1 and DNMT1 to chromatin, acetylates DNA repair proteins, down-regulates NuRD and induces apoptosis in human leukemia and lymphoma cells","volume":"9","author":"Valdez","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.exphem.2018.08.002_bib0031","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.bbmt.2014.08.003","article-title":"Synergistic cytotoxicity of sorafenib with busulfan and nucleoside analogs in human FMS-like tyrosine kinase 3 internal tandem duplications-positive acute myeloid leukemia cells","volume":"20","author":"Song","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"10.1016\/j.exphem.2018.08.002_bib0032","first-page":"3074","article-title":"Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia","volume":"93","author":"Kiyoi","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0033","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nm0795-686","article-title":"5\u2032 CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16\/CDKN2\/MTS1 in human cancers","volume":"1","author":"Merlo","year":"1995","journal-title":"Nat Med"},{"key":"10.1016\/j.exphem.2018.08.002_bib0034","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation","volume":"421","author":"Bakkenist","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.exphem.2018.08.002_bib0035","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/sj.cdd.4401161","article-title":"Degradation of chromosomal DNA during apoptosis","volume":"10","author":"Nagata","year":"2003","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.exphem.2018.08.002_bib0036","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0092-8674(00)80085-9","article-title":"Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c","volume":"86","author":"Liu","year":"1996","journal-title":"Cell"},{"key":"10.1016\/j.exphem.2018.08.002_bib0037","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1023\/A:1022945107762","article-title":"The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update","volume":"8","author":"Ly","year":"2003","journal-title":"Apoptosis"},{"key":"10.1016\/j.exphem.2018.08.002_bib0038","article-title":"Mitochondria-ros crosstalk in the control of cell death and aging","volume":"2012","author":"Marchi","year":"2012","journal-title":"J Signal Transduct"},{"key":"10.1016\/j.exphem.2018.08.002_bib0039","doi-asserted-by":"crossref","first-page":"6993","DOI":"10.1073\/pnas.81.22.6993","article-title":"Covalent bond formation between a DNA cytosine methyltransferase and DNA containing 5-azacytosine","volume":"81","author":"Santi","year":"1984","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.exphem.2018.08.002_bib0040","doi-asserted-by":"crossref","first-page":"11797","DOI":"10.1073\/pnas.91.25.11797","article-title":"Toxicity of 5-aza-2\u2032-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation","volume":"91","author":"J\u00fcttermann","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.exphem.2018.08.002_bib0041","first-page":"1911","article-title":"Internal tandem duplication of the flt3 gene found in acute myeloid leukemia","volume":"10","author":"Nakao","year":"1996","journal-title":"Leukemia"},{"key":"10.1016\/j.exphem.2018.08.002_bib0042","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2002-02-0492","article-title":"The roles of FLT3 in hematopoiesis and leukemia","volume":"100","author":"Gilliland","year":"2002","journal-title":"Blood"},{"key":"10.1016\/j.exphem.2018.08.002_bib0043","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.celrep.2015.06.069","article-title":"Chronic FLT3-ITD Signaling in acute myeloid leukemia is connected to a specific chromatin signature","volume":"12","author":"Cauchy","year":"2015","journal-title":"Cell Rep"},{"key":"10.1016\/j.exphem.2018.08.002_bib0044","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1128\/MCB.01799-07","article-title":"DNA methylation inhibitor 5-Aza-2\u2032-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B","volume":"28","author":"Palii","year":"2008","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.exphem.2018.08.002_bib0045","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/em.20603","article-title":"Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignancies","volume":"51","author":"Valdez","year":"2010","journal-title":"Environ Mol Mutagen"},{"key":"10.1016\/j.exphem.2018.08.002_bib0046","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bcp.2010.09.027","article-title":"The synergistic cytotoxicity of clofarabine, fludarabine and busulfan in AML cells involves ATM pathway activation and chromatin remodeling","volume":"81","author":"Valdez","year":"2011","journal-title":"Biochem Pharmacol"}],"container-title":["Experimental Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0301472X18307495?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0301472X18307495?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T08:33:09Z","timestamp":1759566789000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0301472X18307495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":46,"alternative-id":["S0301472X18307495"],"URL":"https:\/\/doi.org\/10.1016\/j.exphem.2018.08.002","relation":{},"ISSN":["0301-472X"],"issn-type":[{"value":"0301-472X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Epigenetic modification enhances the cytotoxicity of busulfan and4-hydroperoxycyclophosphamide in AML cells","name":"articletitle","label":"Article Title"},{"value":"Experimental Hematology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exphem.2018.08.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc. on behalf of ISEH -- Society for Hematology and Stem Cells.","name":"copyright","label":"Copyright"}]}}