Modeling Global Genomic Instability in Chronic Myeloid Leukemia (CML) Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs).

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37174060", "kind": "science-record", "revision": 4, "content_hash": "sha256:c77a3cc055cc205e603e89bec4bc9c4a2cb16a40219d4c162a91a675352d417c", "created_at": "2026-11-01T19:01:50Z", "updated_at": "2026-11-01T22:51:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Modeling Global Genomic Instability in Chronic Myeloid Leukemia (CML) Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs).", "doi": "10.3390/cancers15092594", "pmid": "37174060", "authors": ["Gladys Telliam", "Christophe Desterke", "Jusuf Imeri", "Radhia M'kacher", "Noufissa Oudrhiri", "Estelle Balducci", "Micheline Fontaine-Arnoux", "Hervé Acloque", "Annelise Bennaceur-Griscelli", "Ali G Turhan"], "journal": "Cancers", "year": 2023, "abstract": "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 γ-H2AX and micronuclei assays and CGH array for genomic events.\nRESULTS: 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "On 249 candidate genes, a supervised one-way ANOVA analysis was performed between the three phases of the disease (with 1000 permutations and p-value threshold less than 1e−3). This analysis identified 125 genes, and an unsupervised principal component analysis allowed us to obtain a very significant group discrimination (p-value of discrimination 9.43e−32; Figure 8A and Supplementary Table S3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37174060", "locator": "sections[21] \"3.4. Comparison of Genomic Aberrations Identified by CGH in CML-iPSC as Compared to Primary Leukemic Blast Crisis Gene Profiling\" paragraph 2", "quote": "On 249 candidate genes, a supervised one-way ANOVA analysis was performed between the three phases of the disease (with 1000 permutations and p-value threshold less than 1e−3). This analysis identified 125 genes, and an unsupervised principal component analysis allowed us to obtain a very significant group discrimination (p-value of discrimination 9.43e−32; Figure 8A and Supplementary Table S3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Not applicable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37174060", "locator": "sections[29] \"notes\" paragraph 1", "quote": "Not applicable."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The transcriptome dataset GSE4170 allowed the authors to associate 125 of 249 detected aberrations in CML-iPSCs with genes associated with CML progression from chronic and accelerated phase to blast crisis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37174060", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The transcriptome dataset GSE4170 allowed the authors to associate 125 of 249 detected aberrations in CML-iPSCs with genes associated with CML progression from chronic and accelerated phase to blast crisis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37174060"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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