{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T04:06:30Z","timestamp":1749701190288,"version":"3.41.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","award":["F\u201012148","F\u201013102"],"award-info":[{"award-number":["F\u201012148","F\u201013102"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["182524","190175\u20102017","208012","303445"],"award-info":[{"award-number":["182524","190175\u20102017","208012","303445"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Resazurin, a phenoxazine used in cell viability assays, acts in\u00a0vitro as an anti\u2010leukaemic compound through the production of cellular reactive oxygen species (ROS) resulting in mitochondrial dysfunction and cell death. However, the in\u00a0vivo tolerance and efficacy of resazurin in cancer are unknown. In this study, we investigated the in\u00a0vitro and in\u00a0vivo effects of resazurin in acute myeloid leukaemia (AML). Resazurininduced cell death in a dose\u2010dependent manner in AML cell lines and reduced proliferation and colony formation in ex\u00a0vivo treated patient\u2010derived AML cells. Cells treated with a reduced dose of resazurin for 72\u2009h acquired a more mature immunophenotype suggesting cell differentiation as a mechanism contributing to the anti\u2010leukaemic effect. In\u00a0vivo optical imaging in healthy mice demonstrated a reduction of resazurin to resorufin within 30\u2009min and non\u2010detectable after 2\u2009h, supporting dosing twice daily as optimal. In subcutaneous and orthotopic models of MV4\u201011 AML in NOD\/SCID IL2r\u03b3<jats:sup>null<\/jats:sup> mice, anti\u2010tumour effects and an increased survival were found at a dose level of 75\u2009mg\/kg twice daily without observed toxicity. Our results suggest that resazurin represents a novel experimental therapeutic for the treatment of AML.<\/jats:p>","DOI":"10.1111\/bjh.19872","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T04:55:01Z","timestamp":1732510501000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical activity of resazurin in acute myeloid leukaemia"],"prefix":"10.1111","volume":"206","author":[{"given":"Trung Quang","family":"Ha","sequence":"first","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Medicine, Hematology Section Haukeland University Hospital  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-2978","authenticated-orcid":false,"given":"Vibeke","family":"Andresen","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-3667","authenticated-orcid":false,"given":"Bjarte Skoe","family":"Erikstein","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Immunology and Transfusion Medicine Haukeland University Hospital  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Popa","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"KinN Therapeutics AS  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8512-9297","authenticated-orcid":false,"given":"Stein\u2010Erik","family":"Gullaksen","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Medicine, Hematology Section Haukeland University Hospital  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5439-8411","authenticated-orcid":false,"given":"H\u00e5kon","family":"Reikvam","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology Section Haukeland University Hospital  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Leukemia Research Group, Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-4625","authenticated-orcid":false,"given":"Emmet","family":"McCormack","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Medicine, Hematology Section Haukeland University Hospital  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Centre for Pharmacy, Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-9704","authenticated-orcid":false,"given":"Bj\u00f8rn Tore","family":"Gjertsen","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science University of Bergen  Bergen Norway"},{"name":"Department of Medicine, Hematology Section Haukeland University Hospital  Bergen Norway"},{"name":"K.G. Jebsen Centre for Myeloid Blood Cancer, Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013626"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00108-3"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01474-9"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-158518"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01606.x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/s120912347"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22741"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11808-3"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2605.1998.00126.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90396-4"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/54004230"},{"issue":"3","key":"e_1_2_12_16_1","first-page":"473","article-title":"A new fluorometric assay for cytotoxicity measurements in\u2010vitro","volume":"3","author":"Page B","year":"1993","journal-title":"Int J Oncol"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(01)00347-7"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(97)00043-4"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1995.1190"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00093"},{"issue":"5","key":"e_1_2_12_21_1","first-page":"1151","article-title":"Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin\u2010induced stress responses","volume":"35","author":"Fritz G","year":"2009","journal-title":"Int J Oncol"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e328326472e"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(78)90185-0"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2009.09.005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020382"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13050966"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1984.tb06054.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912016587"},{"issue":"2","key":"e_1_2_12_29_1","first-page":"592","article-title":"Characterization of ATM and DNA\u2010PK wild\u2010type and mutant cell lines upon DSB induction in the presence and absence of CK2 inhibitors","volume":"40","author":"Olsen BB","year":"2012","journal-title":"Int J Oncol"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1602"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00567-7"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15143711"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-024-02316-6"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00717-4"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.209"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1734"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15068"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01528-5"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02075-w"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3085-y"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.510495"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.19872","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T06:08:56Z","timestamp":1749622136000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.19872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,24]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/bjh.19872"],"URL":"https:\/\/doi.org\/10.1111\/bjh.19872","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"type":"print","value":"0007-1048"},{"type":"electronic","value":"1365-2141"}],"subject":[],"published":{"date-parts":[[2024,11,24]]},"assertion":[{"value":"2024-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}