{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:40:49Z","timestamp":1790793649478,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic differentiation for their phenotype, clonogenicity, and transcriptomic profile. Single-cell RNA-Seq analysis has been performed at three different time points during hematopoietic differentiation in ENU-treated and untreated cells. Results: One of the CML-iPSCs, compared to its non-mutagenized counterpart, generated myeloid blasts after hematopoietic differentiation, exhibiting monoblastic patterns and expression of cMPO, CD45, CD34, CD33, and CD13. Single-cell transcriptomics revealed a delay of differentiation in the mutated condition as compared to the control with increased levels of MSX1 (mesodermal marker) and a decrease in CD45 and CD41. Bulk transcriptomics analyzed along with the GSE4170 GEO dataset reveal a significant overlap between ENU-treated cells and primary BC cells. Among overexpressed genes, CD25 was identified, and its relevance was confirmed in a cohort of CML patients. Conclusions: iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression.<\/jats:p>","DOI":"10.3390\/cells12040598","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T04:32:58Z","timestamp":1676262778000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-7388","authenticated-orcid":false,"given":"Jusuf","family":"Imeri","sequence":"first","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-2524","authenticated-orcid":false,"given":"Christophe","family":"Desterke","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Marcoux","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gladys","family":"Telliam","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Sanekli","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"APHP Paris Saclay, Department of Hematology, H\u00f4pital Bic\u00eatre & Paul Brousse, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Barreau","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"APHP Paris Saclay, Department of Hematology, H\u00f4pital Bic\u00eatre & Paul Brousse, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-6649","authenticated-orcid":false,"given":"Yucel","family":"Erbilgin","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Latsis","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Hugues","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Sorel","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"Service de Canc\u00e9rologie Biologique, CHU de Poitiers, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Cayssials","sequence":"additional","affiliation":[{"name":"Service d\u2019Oncologie H\u00e9matologique et Th\u00e9rapie Cellulaire, CHU de Poitiers, 86021 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Chomel","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"Service de Canc\u00e9rologie Biologique, CHU de Poitiers, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-4499","authenticated-orcid":false,"given":"Annelise","family":"Bennaceur-Griscelli","sequence":"additional","affiliation":[{"name":"INSERM UMR-S-1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France and ESTeam Paris Sud, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"APHP Paris Saclay, Department of Hematology, H\u00f4pital Bic\u00eatre & Paul Brousse, 94800 Villejuif, France"},{"name":"INGESTEM National iPSC Infrastructure, 94800 Villejuif, France"},{"name":"CITHERA, Centre for iPSC Therapies, INSERM UMS-45, Genopole Campus, 91100 Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-0137","authenticated-orcid":false,"given":"Ali G.","family":"Turhan","sequence":"additional","affiliation":[{"name":"INSERM 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