Evidence map›Paper›PMID 41758310›Full record

ArticleGenes & genomics2026

Glycolytic-inflammatory crosstalk mediated by Glyco-PMF-Rux hub genes drives PMF progression and ruxolitinib resistance.

Shujing Zhang, Muhammad Sameer Ashaq, Yi Wang, Yuan Li, Baobing Zhao

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In one paragraph

Article in Genes & genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Shujing ZhangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Muhammad Sameer AshaqState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Yi WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Yuan LiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Baobing ZhaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China. baobingzh@sdu.edu.cn.ORCID http://orcid.org/0000-0001-8522-4764

Funding

National Key Research and Development Program of China 2024YFC2510500the key Program of Innovation Improvement of Small and Medium-sized Enterprises of Shandong Province in China 2023TSGC0717
6 · The paper itself

Abstract

backgroundPrimary myelofibrosis (PMF) is an aggressive myeloproliferative neoplasm characterized by bone marrow fibrosis, chronic inflammation, and high leukemic risk. Although ruxolitinib (Rux) is a first-line therapy, nearly half of patients develop resistance within three years. Glycolytic reprogramming contributes to inflammatory signaling and drug resistance, while the link between metabolic reprogramming and Rux resistance remains unclear.

objectiveThis study aims to identify key genes involved in glycolytic-inflammatory crosstalk driving PMF progression and Rux resistance, with the goal of evaluating their potential as diagnostic and therapeutic targets.

methodsWe integrated multiple GEO datasets to identify differentially expressed genes (DEGs) related to PMF, Rux resistance, and glycolysis. A total of 75 overlapping DEGs were identified. Protein-protein interaction analysis and centrality measures revealed four key hub genes: STAT1, EGR1, FOXO1 and SMAD7. Their diagnostic and functional relevance was assessed using GO/KEGG enrichment, ROC analysis, single-cell RNA-seq and immune infiltration analysis.

resultsAll four hub genes were significantly dysregulated and showed potential diagnostic value. Functional enrichment highlighted pathways of inflammation, apoptosis, and metabolic reprogramming. Single-cell analysis revealed their enrichment in hematopoietic stem/progenitor cells and correlation with resistance markers. STAT1/EGR1 were associated with pro-inflammatory immune cells, while FOXO1/SMAD7 were linked to immune evasion. Notably, STAT1 and EGR1 were significantly upregulated in ruxolitinib-resistant HEL cells. Functional assays demonstrated that STAT1 knockdown suppressed the proliferation of resistant cells, while EGR1 was further validated by its significant upregulation in PMF mouse models.

conclusionsSTAT1, EGR1, FOXO1, and SMAD7 are associated with glycolytic-inflammatory crosstalk underlying PMF progression and ruxolitinib resistance, with experimental validation supporting STAT1 and EGR1 as potential diagnostic and therapeutic targets.

Indexed as

Drug Resistance, NeoplasmGlycolysisNitrilesPyrazolesAnimalsDisease ProgressionEarly Growth Response Protein 1Forkhead Box Protein O1HumansInflammationProtein Interaction MapsPyrimidinesSmad7 ProteinSTAT1 Transcription FactorEarly Growth Response Protein 1Forkhead Box Protein O1NitrilesPyrazolesPyrimidinesruxolitinibSmad7 ProteinSTAT1 Transcription FactorGlycolytic reprogrammingImmune microenvironmentPrimary myelofibrosis (PMF)Ruxolitinib resistanceSingle-cell RNA-seq

Identifiers

PMID41758310

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.