{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:15:43Z","timestamp":1790774143513,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is characterized by blocked differentiation and extensive proliferation of hematopoietic progenitors\/precursors. Relapse is often observed after chemotherapy due to the presence of residual leukemic cells, which is also called minimal residual disease (MRD). Subclonal heterogeneity at diagnosis was found to be responsible for MRD after treatment. Patient xenograft mouse models are valuable tools for studying MRD after chemotherapy; however, the contribution of the immune system in these models is usually missing. To evaluate its role in leukemic persistence, we generated an immune-competent AML mouse model of persistence after chemotherapy treatment. We used well-characterized (phenotypically and genetically) subclones of the murine C1498 cell line stably expressing the<jats:italic>ZsGreen<\/jats:italic>reporter gene and the WT1 protein, a valuable antigen. Accordingly, these subclones were also selected due to their<jats:italic>in vitro<\/jats:italic>aracytidine (Ara-c) sensitivity. A combination of 3 subclones (expressing or not expressing WT1) was found to lead to prolonged mouse survival after Ara-c treatment (as long as 150 days). The presence of residual leukemic cells in the blood and BM of surviving mice indicated their persistence. Thus, a new mouse model that may offer insights into immune contributions to leukemic persistence was developed.<\/jats:p>","DOI":"10.1371\/journal.pone.0267508","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T17:34:29Z","timestamp":1651253669000},"page":"e0267508","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Detection of residual and chemoresistant leukemic cells in an immune-competent mouse model of acute myeloid leukemia: Potential for unravelling their interactions with 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Ishikawa","year":"2007","journal-title":"Nat Biotechnol"},{"issue":"3","key":"pone.0267508.ref011","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1607","article-title":"Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML","volume":"28","author":"Y Saito","year":"2010","journal-title":"Nat Biotechnol"},{"issue":"7437","key":"pone.0267508.ref012","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature11824","article-title":"T-helper-1-cell cytokines drive cancer into senescence","volume":"494","author":"H Braum\u00fcller","year":"2013","journal-title":"Nature"},{"issue":"6","key":"pone.0267508.ref013","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1172\/JCI42002","article-title":"Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma","volume":"120","author":"J Eyles","year":"2010","journal-title":"J Clin 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model","volume":"116","author":"A Mopin","year":"2016","journal-title":"J Vis Exp"},{"key":"pone.0267508.ref024","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.imlet.2017.10.004","article-title":"Sub-clonal analysis of the murine C1498 acute myeloid leukaemia cell line reveals genomic and immunogenic diversity","volume":"192","author":"V Driss","year":"2017","journal-title":"Immunol Lett"},{"issue":"10","key":"pone.0267508.ref025","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1038\/leu.2012.145","article-title":"Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia","volume":"26","author":"S Anguille","year":"2012","journal-title":"Leukemia"},{"issue":"31","key":"pone.0267508.ref026","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1200\/JCO.2009.22.4865","article-title":"Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a european leukemianet study","volume":"27","author":"D Cilloni","year":"2009","journal-title":"J Clin Oncol"},{"issue":"24","key":"pone.0267508.ref027","doi-asserted-by":"crossref","first-page":"8799","DOI":"10.1158\/1078-0432.CCR-05-1314","article-title":"T-cell responses directed against multiple HLA-A*0201-restricted epitopes derived from Wilm\u2019s tumor 1 protein in patients with leukemia and healthy donors: identification, quantification, and characterization","volume":"11","author":"K Rezvani","year":"2005","journal-title":"Clin Cancer Res"},{"issue":"12","key":"pone.0267508.ref028","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1182\/blood-2017-09-801498","article-title":"Minimal\/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party","volume":"131","author":"GJ Schuurhuis","year":"2018","journal-title":"Blood"},{"issue":"1","key":"pone.0267508.ref029","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/mus.21809","article-title":"Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy","volume":"43","author":"LAA Gilliam","year":"2011","journal-title":"Muscle Nerve"},{"issue":"2","key":"pone.0267508.ref030","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/eji.201444736","article-title":"Monocyte chemoattractant protein 1 (MCP-1\/CCL2) contributes to thymus atrophy in acute myeloid leukemia","volume":"45","author":"V Driss","year":"2015","journal-title":"Eur J Immunol"},{"issue":"3","key":"pone.0267508.ref031","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3324\/haematol.2015.131946","article-title":"Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial","volume":"101","author":"C Willekens","year":"2016","journal-title":"Haematologica"},{"issue":"11","key":"pone.0267508.ref032","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1182\/blood-2009-03-213389","article-title":"Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML","volume":"114","author":"S Schnittger","year":"2009","journal-title":"Blood"},{"issue":"11","key":"pone.0267508.ref033","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/ncb2861","article-title":"TGF-\u03b22 dictates disseminated tumour cell fate in target organs through TGF\u03b2-RIII and p38\u03b1\/\u03b2 signalling","volume":"15","author":"P Bragado","year":"2013","journal-title":"Nat Cell Biol"},{"issue":"2","key":"pone.0267508.ref034","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"AB 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