{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:40:52Z","timestamp":1790793652617,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Methods: We used a patient-specific induced pluripotent stem cell (iPSC) line treated with the mutagenic agent N-ethyl-N-nitrosourea (ENU). Genomic instability was validated using \u03b3-H2AX and micronuclei assays and CGH array for genomic events. Results: An increased number of progenitors (x5-Fold), which proliferated in liquid cultures with a blast cell morphology, was observed in the mutagenized condition as compared to the unmutagenized one. CGH array performed for both conditions in two different time points reveals several cancer genes in the ENU-treated condition, some known to be altered in leukemia (BLM, IKZF1, NCOA2, ALK, EP300, ERG, MKL1, PHF6 and TET1). Transcriptome GEO-dataset GSE4170 allowed us to associate 125 of 249 of the aberrations that we detected in CML-iPSC with the CML progression genes already described during progression from chronic and AP to BC. Among these candidates, eleven of them have been described in CML and related to tyrosine kinase inhibitor resistance and genomic instability. Conclusions: These results demonstrated that we have generated, for the first time to our knowledge, an in vitro genetic instability model, reproducing genomic events described in patients with BC.<\/jats:p>","DOI":"10.3390\/cancers15092594","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:33:36Z","timestamp":1683164016000},"page":"2594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Modeling Global Genomic Instability in Chronic Myeloid Leukemia (CML) Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)"],"prefix":"10.3390","volume":"15","author":[{"given":"Gladys","family":"Telliam","sequence":"first","affiliation":[{"name":"INSERM UMR_S_1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"Facult\u00e9 de M\u00e9decine Paris Saclay, Universit\u00e9 Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, 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"},{"name":"Facult\u00e9 de M\u00e9decine Paris Saclay, Universit\u00e9 Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-7388","authenticated-orcid":false,"given":"Jusuf","family":"Imeri","sequence":"additional","affiliation":[{"name":"INSERM UMR_S_1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-4760","authenticated-orcid":false,"given":"Radhia","family":"M\u2019kacher","sequence":"additional","affiliation":[{"name":"APHP Paris Saclay Service d\u2019Oncoh\u00e9matologie 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H\u00f4pital Paul Brousse, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheline","family":"Fontaine-Arnoux","sequence":"additional","affiliation":[{"name":"APHP Paris Saclay Service d\u2019Oncoh\u00e9matologie Mol\u00e9culaire et Cytog\u00e9n\u00e9tique H\u00f4pital Paul Brousse, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Acloque","sequence":"additional","affiliation":[{"name":"INSERM UMR_S_1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, 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"},{"name":"Facult\u00e9 de M\u00e9decine Paris Saclay, Universit\u00e9 Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"APHP Paris Saclay Service d\u2019Oncoh\u00e9matologie Mol\u00e9culaire et Cytog\u00e9n\u00e9tique H\u00f4pital Paul Brousse, 94800 Villejuif, France"},{"name":"APHP-Paris Saclay Service d\u2019H\u00e9matologie-Bic\u00eatre, 94270 Le Kremlin Bic\u00eatre, France"},{"name":"INGESTEM National iPSC Infrastructure, 94800 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, G\u00e9nopole, 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 UMR_S_1310, Universit\u00e9 Paris Saclay, 94800 Villejuif, France"},{"name":"Facult\u00e9 de M\u00e9decine Paris Saclay, Universit\u00e9 Paris Saclay, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"APHP Paris Saclay Service d\u2019Oncoh\u00e9matologie Mol\u00e9culaire et Cytog\u00e9n\u00e9tique H\u00f4pital Paul Brousse, 94800 Villejuif, France"},{"name":"APHP-Paris Saclay Service d\u2019H\u00e9matologie-Bic\u00eatre, 94270 Le Kremlin Bic\u00eatre, France"},{"name":"INGESTEM National iPSC Infrastructure, 94800 Villejuif, France"},{"name":"Centre for iPSC Therapies (CITHERA) INSERM UMS 45, G\u00e9nopole, 91100 Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1038\/leu.2010.159","article-title":"Insights into the Stem Cells of Chronic Myeloid Leukemia","volume":"24","author":"Sloma","year":"2010","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0002-9343(87)90754-6","article-title":"Chronic Myelogenous Leukemia in Blast Crisis. 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