{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:51:13Z","timestamp":1792291873839,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T00:00:00Z","timestamp":1514246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research UK Glasgow Centre","award":["C596\/A18076"],"award-info":[{"award-number":["C596\/A18076"]}]},{"name":"BSU facilities, Cancer Research UK Beatson Institute","award":["C596\/A17196"],"award-info":[{"award-number":["C596\/A17196"]}]},{"DOI":"10.13039\/501100000589","name":"Chief Scientists' Office","doi-asserted-by":"crossref","award":["ETM\/374"],"award-info":[{"award-number":["ETM\/374"]}],"id":[{"id":"10.13039\/501100000589","id-type":"DOI","asserted-by":"crossref"}]},{"name":"William and Elizabeth Davies Foundation"},{"name":"Amber Phillpott Trust, Treating Children with Cancer, the Birmingham Children's Hospital Research Fund"},{"name":"patient and family fundraisers via the University of Birmingham Development and Alumni Relations Team and Cancer Research UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Arginine is a semi\u2010essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT\u2010100, a pegylated (PEG) recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT\u2010100 is cytotoxic to ALL blasts from patients <jats:italic>in vitro<\/jats:italic> by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts, BCT\u2010100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT\u20101, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT\u2010100 cytotoxicity at arginine depleting doses. RNA\u2010sequencing of ALL blasts and supporting stromal cells treated with BCT\u2010100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore, BCT\u2010100 provides a new clinically relevant therapeutic approach to target arginine metabolism in ALL.<\/jats:p>","DOI":"10.1002\/ijc.31170","type":"journal-article","created":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T08:44:40Z","timestamp":1511426680000},"page":"1490-1502","source":"Crossref","is-referenced-by-count":65,"title":["The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated\u2010recombinant arginase I BCT\u2010100"],"prefix":"10.1002","volume":"142","author":[{"given":"Carmela","family":"De Santo","sequence":"first","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Booth","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Vardon","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Cousins","sequence":"additional","affiliation":[{"name":"Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Tubb","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Perry","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Noyvert","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Beggs","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology The Chinese University of Hong Kong  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Halsey","sequence":"additional","affiliation":[{"name":"Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Kearns","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cheng","sequence":"additional","affiliation":[{"name":"Bio\u2010Cancer Treatment International Ltd  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-0047","authenticated-orcid":false,"given":"Francis","family":"Mussai","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy, University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2016.1237939"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116582"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70265-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2004.03.005"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3360001"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30051"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1945"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0200-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-600643"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0655"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-665034"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-480129"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70274-7"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.359"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600681"},{"key":"e_1_2_6_20_1","first-page":"2980","article-title":"Nitric oxide alters the expression of gamma\u2010globin, H\u2010ferritin, and transferrin receptor in human K562 cells at the posttranscriptional level","volume":"88","author":"Domachowske JB","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_21_1","first-page":"632","article-title":"BCR\u2010ABL1 and CD66c exhibit high concordance in minimal residual disease detection of adult B\u2010acute lymphoblastic leukemia. 2015","volume":"7","author":"Tang GS","year":"2015","journal-title":"Am J Transl Res"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190109097660"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1491"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082859"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.411"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70243-8"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.524"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(92)90173-5"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06763.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.197"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049-3002-1-12"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15529"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1606022113"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2011.1391"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.72.1.241"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.42.978"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/2162-3619-2-11"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.618769"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.10.001"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1267"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20100451"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12865"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-012-9807-9"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.7765"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2610"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.3049"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.31170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.31170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T19:44:09Z","timestamp":1703274249000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.31170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,26]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/ijc.31170"],"URL":"https:\/\/doi.org\/10.1002\/ijc.31170","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,26]]}}}