High expression of malic enzyme 1 predicts adverse prognosis in patients with cytogenetically normal acute myeloid leukaemia and promotes leukaemogenesis through the IL-6/JAK2/STAT3 pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39610460", "kind": "science-record", "revision": 3, "content_hash": "sha256:8b65e6d2dc6455ca0d7047b290d88409ed12e5b53f11801d4dc36d37bdf5eeb9", "created_at": "2026-11-01T20:29:52Z", "updated_at": "2026-11-01T22:13:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High expression of malic enzyme 1 predicts adverse prognosis in patients with cytogenetically normal acute myeloid leukaemia and promotes leukaemogenesis through the IL-6/JAK2/STAT3 pathways.", "doi": "10.1177/20406207241301948", "pmid": "39610460", "authors": ["Chang Zhang", "Wenlu Li", "Fei Wu", "Zhongwei Lu", "Piaorong Zeng", "Zeyu Luo", "Yixiong Cao", "Feng Wen", "Junjun Li", "Xi Chen", "Fujue Wang"], "journal": "Therapeutic advances in hematology", "year": 2024, "abstract": "Background: Progress in improving risk stratification methods for patients with cytogenetically normal acute myeloid leukaemia (CN-AML) remains limited. This study investigates the prognostic significance and potential functional mechanism of malic enzyme 1 (ME1) in CN-AML.\nMethods: Gene expression and clinical data of patients with CN-AML were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, which were subjected to analysis. The prognostic significance of ME1 was assessed through Kaplan-Meier survival analysis, as well as univariate and multivariate Cox regression analyses. A novel risk model based on ME1 expression levels was developed using TCGA data for predicting CN-AML prognosis. Furthermore, the impact of ME1 silencing on AML cell lines was investigated using the Cell Counting Kit-8 assay and flow cytometry. Gene set enrichment analysis (GSEA) analysis and Western blotting were performed to explore the mechanism of ME1 in CN-AML.\nResults: CN-AML patients expressing higher ME1 levels exhibited shorter event-free survival (EFS) and overall survival (OS) compared to those with lower ME1 expression in the TCGA and multiple GEO datasets (all p < 0.05). Univariate and multivariate Cox regression analyses indicated that ME1 expression served as an independent prognostic factor for the EFS (p = 0.024 in TCGA, p = 0.035 in GSE6891) and OS (p = 0.039 in TCGA, p = 0.008 in GSE6891) in patients with CN-AML. The developed risk model demonstrated that patients with CN-AML in the high-risk group had worse survival than those in the low-risk group (hazard ratio: 2.67, 95% confidence interval: 1.54-4.65, p < 0.001) and exhibited strong predictive accuracy for 1-, 3- and 5-year OS (area under the curve = 0.69, 0.75, 0.79, respectively). ME1 knockdown significantly inhibited proliferation and increased apoptosis in AML cells (all p < 0.05). GSEA and Western blotting demonstrated that ME1 regulates the IL-6/JAK2/STAT3 pathway in CN-AML.\nConclusion: Elevated ME1 expression serves as an indicator of poorer prognosis in patients with CN-AML, potentially facilitating leukaemogenesis through the IL-6/JAK2/STAT3 pathway. This suggests that ME1 could be a promising prognostic biomarker and therapeutic target for CN-AML.", "claims": [{"id": "claim-data-access", "statement": "All the databases or datasets used in this study can be found in online repositories with corresponding websites mentioned in the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39610460", "locator": "sections[24] \"Declarations\" paragraph 2", "quote": "All the databases or datasets used in this study can be found in online repositories with corresponding websites mentioned in the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ME1 expression was an independent prognostic factor for EFS and OS in patients with CN-AML.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39610460", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Univariate and multivariate Cox regression analyses indicated that ME1 expression served as an independent prognostic factor for the EFS (p = 0.024 in TCGA, p = 0.035 in GSE6891) and OS (p = 0.039 in TCGA, p = 0.008 in GSE6891) in patients with CN-AML."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ME1 expression was an independent prognostic factor for EFS and OS in patients with CN-AML.", "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:39610460"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12417"], "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:GSE12417"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39610460", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1177/20406207241301948", "sha256": 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