Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs).

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36831265", "kind": "science-record", "revision": 3, "content_hash": "sha256:722247c8727176dffe0b8cdc73f747be43617b1b8db457dd120b7720dcb50842", "created_at": "2026-11-01T19:01:26Z", "updated_at": "2026-11-01T22:08:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs).", "doi": "10.3390/cells12040598", "pmid": "36831265", "authors": ["Jusuf Imeri", "Christophe Desterke", "Paul Marcoux", "Gladys Telliam", "Safa Sanekli", "Sylvain Barreau", "Yucel Erbilgin", "Theodoros Latsis", "Patricia Hugues", "Nathalie Sorel", "Emilie Cayssials", "Jean-Claude Chomel", "Annelise Bennaceur-Griscelli", "Ali G Turhan"], "journal": "Cells", "year": 2023, "abstract": "PURPOSE: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "This machine learning analysis was performed with pamr R-package version 1.56.1 by leaving one out cross-validation process [35].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36831265", "locator": "sections[18] \"2.16. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE4170"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE4170"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36831265", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cells12040598", "sha256": 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