{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:03:02Z","timestamp":1771372982247,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T00:00:00Z","timestamp":1361232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosome\u2013positive acute lymphoblastic leukaemia (Ph<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>) still remains poor. Because most adults eventually relapse without allogeneic stem cell transplantation, which is not available for all patients, novel strategies are required for relapse prevention. As the integrity of the immune system is essential for the control of remaining leukaemia cells, we compared the efficacy of anthocyanins, imatinib and a <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010based vaccine as non\u2010immunosuppressant components with 6\u2010mercaptopurine (6\u2010<jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>) to control minimal residual disease <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> using different leukaemia cell lines and syngeneic mice. Proliferation of Ph<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> was significantly better inhibited by anthocyanin\u2010rich berry extract or imatinib compared with 6\u2010<jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>. Although anthocyanins induced apoptosis in some leukaemia cell lines, the level of caspase\u20103, caspase\u20108 and caspase\u20109 was significantly lower compared with imatinib and 6\u2010<jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content>. When used as single components, anthocyanins and imatinib mesylate failed to eradicate pre\u2010existing Ph<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> in syngeneic mice, while 6\u2010<jats:styled-content style=\"fixed-case\">MP<\/jats:styled-content> led to 10% and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> vaccination to 56% survival. Intriguingly, only the combination of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> vaccination with berry extract but not with the isolated anthocyanin, cyanidin\u20103\u2010rutinoside or imatinib further increased leukaemia\u2010free and overall survival, and 90% of lethally challenged mice survived. We suggest that induction and enhancement of a leukaemia\u2010specific immunity by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> vaccination and anthocyanin\u2010rich berry extract can also decrease the relapse rate in patients with Ph<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>. Furthermore, this approach may serve as strategy for maintenance therapy of other malignancies.<\/jats:p>","DOI":"10.1111\/ejh.12071","type":"journal-article","created":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T18:51:27Z","timestamp":1357584687000},"page":"291-300","source":"Crossref","is-referenced-by-count":6,"title":["Can anthocyanins improve maintenance therapy of Ph<sup>+<\/sup> acute lymphoblastic leukaemia?"],"prefix":"10.1111","volume":"90","author":[{"given":"Joachim","family":"K\u00f6chling","sequence":"first","affiliation":[{"name":"Department of Paediatrics UKSH Campus L\u00fcbeck Universit\u00e4t zu L\u00fcbeck Germany"},{"name":"Department of Paediatric Oncology and Haematology Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Mologen AG Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Rott","sequence":"additional","affiliation":[{"name":"Department of Paediatrics UKSH Campus L\u00fcbeck Universit\u00e4t zu L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sagner","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention University Cancer Center Hamburg Hamburg Germany"},{"name":"Department of Sports Medicine University Hospital Eppendorf Hamburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Ungefroren","sequence":"additional","affiliation":[{"name":"First Department of Medicine UKSH Campus L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burghard","family":"Wittig","sequence":"additional","affiliation":[{"name":"Foundation Institute Molecular Biology and Bioinformatics Freie Universit\u00e4t Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Henze","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology and Haematology Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-01-199380"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.1287"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-112920"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.2514"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200004063421402"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-052373"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09883"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2009.1.371"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25136"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.5.1572.005k12_1572_1579"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.06.094"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.07.037"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1251-4"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-187880"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.042036"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712800672102"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdi361"},{"key":"e_1_2_7_19_1","unstructured":"American Institute for Cancer Research.2012. Available from:http:\/\/www.aicr.org\/."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2003.07.004"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh138"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600861200"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.03.023"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2232"},{"key":"e_1_2_7_25_1","first-page":"297","article-title":"Cyanidin 3\u2010O\u2010beta\u2010D\u2010glucoside isolated from skin of black Glycine max and other anthocyanins isolated from skin of red grape induce apoptosis in human lymphoid leukemia Molt 4B cells","volume":"10","author":"Katsuzaki H","year":"2003","journal-title":"Oncol Rep"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610616200"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.14-2049"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.5.1866"},{"key":"e_1_2_7_29_1","first-page":"3142","article-title":"Protection of mice against Ph+ acute lymphoblastic leukemia by cell\u2010based vaccination using non\u2010viral, minimalistic expression vectors and immunomodulatory oligonucleotides","volume":"9","author":"K\u00f6chling J","year":"2003","journal-title":"Clin Can Res"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2001.0322"},{"key":"e_1_2_7_31_1","first-page":"67","article-title":"Selected strategies to augment polynucleotide immunization","volume":"3","author":"Conry RM","year":"1996","journal-title":"Gene Ther"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1997.8.11-1303"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2005.00908.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31414"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.553187"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1816"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2113314"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.9.2507.bloodjournal8592507"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404146"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0352778"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.06.009"},{"key":"e_1_2_7_42_1","first-page":"1077","article-title":"Induction of apoptosis in human leukemia U937 cells by anthocyanins through down\u2010regulation of Bcl\u20102 and activation of caspases","volume":"34","author":"Lee SH","year":"2009","journal-title":"Int J Oncol"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-0976-y"},{"key":"e_1_2_7_44_1","first-page":"1471","article-title":"Anthocyanins are novel AMPK\u03b11 stimulators that suppress tumor growth by inhibiting mTOR phosphorylation","volume":"24","author":"Lee YK","year":"2010","journal-title":"Oncol Rep"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-0996-7"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206091"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1343"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050195"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950017103"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2010.04.002"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2028"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-011-1096-1"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5401_2"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100526"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005279636"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.05.020"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejh.12071","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.12071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T01:30:12Z","timestamp":1697592612000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.12071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,19]]},"references-count":55,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1111\/ejh.12071"],"URL":"https:\/\/doi.org\/10.1111\/ejh.12071","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,19]]}}}