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http://purl.uniprot.org/citations/24747972http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24747972http://www.w3.org/2000/01/rdf-schema#comment"Relapse of chronic myeloid leukemia (CML) is triggered by stem cells with a reconstituting capacity similar to that of hematopoietic stem cells (HSCs) and CML stem cells are a source of resistance in drug therapy with tyrosine kinase inhibitors (TKIs). Ecotropic viral integration site 1 (EVI1), a key transcription factor in HSC regulation, is known to predict poor outcomes in myeloid malignancies, however, incapability of prospective isolation of EVI1-high leukemic cells precludes the functional evaluation of intraindividual EVI1-high cells. Introduction of CML into Evi1-internal ribosomal entry site (IRES)-green fluorescent protein (GFP) knock-in mice, a versatile HSC-reporter strain, enables us to separate Evi1-high CML cells from the individual. Evi1-IRES-GFP allele models of CML in chronic phase (CML-CP), by retroviral overexpression of BCR-ABL and by crossing BCR-ABL transgenic mice, revealed that Evi1 is predominantly enriched in the stem cell fraction and associated with an enhanced proliferative as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit resistance to TKIs. Overexpressing BCR-ABL and NUP98-HOXA9 in Evi1-IRES-GFP knock-in mice to model CML in blast crisis (CML-BC), in which Evi1-high cells turned to be a major population as opposed to a minor population in CML-CP models, showed that Evi1-high CML-BC cells have a greater potential to recapitulate the disease and appear resistant to TKIs. Furthermore, given that Evi1 heterozygosity ameliorates CML-CP and CML-BC development and that the combination of Evi1 and BCR-ABL causes acute myeloid leukemia resembling CML-BC, Evi1 could regulate CML development as a potent driver. In addition, in human CML-CP cases, we show that EVI1 is highly expressed in stem cell-enriched CD34+CD38-CD90+ fraction at single-cell level. This is the first report to clarify directly that Evi1-high leukemic cells themselves possess the superior potential to Evi1-low cells in oncogenic self-renewal, which highlights the role of Evi1 as a valuable and a functional marker of CML stem cells."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.org/dc/terms/identifier"doi:10.1038/onc.2014.108"xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Arai S."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kataoka K."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Nakagawa M."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Sato T."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kadowaki T."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kubota N."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Yoshimi A."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Goyama S."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kurokawa M."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Honda H."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kumagai K."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Kagoya Y."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Nasu R."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Nukina A."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/author"Tsuruta-Kishino T."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/name"Oncogene"xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/pages"5028-5038"xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/title"Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia."xsd:string
http://purl.uniprot.org/citations/24747972http://purl.uniprot.org/core/volume"33"xsd:string
http://purl.uniprot.org/citations/24747972http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24747972
http://purl.uniprot.org/citations/24747972http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24747972
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