Exploring redox vulnerabilities in JAK2V617F-positive cellular models.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32962959", "kind": "science-record", "revision": 9, "content_hash": "sha256:8657f24796c5ad8a0c43cee550ff92656605a4a517fdf457f310d3573c5c09f1", "created_at": "2026-11-01T15:41:11Z", "updated_at": "2026-11-01T22:45:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring redox vulnerabilities in JAK2V617F-positive cellular models.", "doi": "10.1016/j.htct.2020.08.006", "pmid": "32962959", "authors": ["Keli Lima", "Lucia Rossetti Lopes", "João Agostinho Machado-Neto"], "journal": "Hematology, transfusion and cell therapy", "year": 2021, "abstract": "BACKGROUND: In Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) models, reactive oxygen species (ROS) are elevated and have been implicated in genomic instability, JAK2/STAT signaling amplification, and disease progression. Although the potential effects of ROS on the MPN phenotype, the effects of ruxolitinib treatment on ROS regulation have been poorly explored. Herein, we have reported the impact of ruxolitinib on redox signaling transcriptional network, and the effects of diphenyleneiodonium (DPI), a pan NOX inhibitor, in JAK2V617F-driven cellular models.\nMETHOD: Redox signaling-related genes were investigated in SET2 cells upon ruxolitinib treatment by RNA-seq (GEO accession GSE69827). SET2 and HEL cells, which represent JAK2V617F-positive MPN cellular models with distinct sensitivity to apoptosis induced by ruxolitinib, were used. Cell viability was evaluated by MTT, apoptosis by annexin V/PI and flow cytometry, and cell signaling by quantitative PCR and Western blot.\nMAIN RESULTS: Ruxolitinib impacted on a network composed of redox signaling-related genes, and DUOX1 and DUOX2 were identified as potential modulators of ruxolitinib response. In SET2 and HEL cells, DPI reduced cell viability and, at low doses, it significantly potentiated ruxolitinib-induced apoptosis. In the molecular scenario, DPI inhibited STAT3, STAT5 and S6 ribosomal protein phosphorylation and induced PARP1 cleavage in JAK2V617F-positive cells. DPI combined with ruxolitinib increased PARP1 cleavage in SET2 cells and potentiated ruxolitinib-reduced STAT3, STAT5 and S6 ribosomal protein in HEL cells.\nCONCLUSION: Our study reveals a potential adaptation mechanism for resistance against ruxolitinib by transcriptionally reprogramming redox signaling in JAK2V617F cells and exposes redox vulnerabilities with therapeutic value in MPN cellular models.", "claims": [{"id": "claim-method", "statement": "For comparisons, ANOVA test and Bonferroni post-test or Student t-test were used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32962959", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "For comparisons, ANOVA test and Bonferroni post-test or Student t-test were used."}], "state": "complete"}, {"id": "claim-data-access", "statement": "RNA-seq data were obtained from Meyer et al.14 (https://www.ncbi.nlm.nih.gov/geo; GEO accession GSE69827). The expression of 81 redox signaling-related genes in samples from naïve SET2 cells (GSM1817344, GSM1817345, and GSM1817346) and ruxolitinib-treated SET2 cells (GSM1817332, GSM1817333, and GSM1817334) was investigated.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32962959", "locator": "sections[3] \"RNA-seq data analysis\" paragraph 2", "quote": "RNA-seq data were obtained from Meyer et al.14 (https://www.ncbi.nlm.nih.gov/geo; GEO accession GSE69827). The expression of 81 redox signaling-related genes in samples from naïve SET2 cells (GSM1817344, GSM1817345, and GSM1817346) and ruxolitinib-treated SET2 cells (GSM1817332, GSM1817333, and GSM1817334) was investigated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:32962959"], "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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The expression of 81 redox signaling-related genes in samples from naïve SET2 cells (GSM1817344, GSM1817345, and GSM1817346) and ruxolitinib-treated SET2 cells (GSM1817332, GSM1817333, and GSM1817334) was investigated.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "RNA-seq data were obtained from Meyer et al.14 (https://www.ncbi.nlm.nih.gov/geo; GEO accession GSE69827). The expression of 81 redox signaling-related genes in samples from naïve SET2 cells (GSM1817344, GSM1817345, and GSM1817346) and ruxolitinib-treated SET2 cells (GSM1817332, GSM1817333, and GSM1817334) was investigated.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1817323", "GSM1817324", "GSM1817325", "GSM1817326", "GSM1817327", "GSM1817328", "GSM1817329", "GSM1817330", "GSM1817331", "GSM1817332", "GSM1817333", "GSM1817334", "GSM1817335", "GSM1817336", "GSM1817337", "GSM1817338", "GSM1817339", "GSM1817340", "GSM1817341", "GSM1817342", "GSM1817343", "GSM1817344", "GSM1817345", "GSM1817346"], "sample_count": 24, "group_sizes": null, "group_sizes_basis": null, "platform": "17303", "taxon": "Homo sapiens", "title": "Differential expression profiles of type I JAK inhibitor persistent vs. naïve MPN cells", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE69827 not downloaded", "asset:data:geo:GSE69827 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "For comparisons, ANOVA test and Bonferroni post-test or Student t-test were used."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student t-test"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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