{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:25:51Z","timestamp":1769837151529,"version":"3.49.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The prognostic management of acute myeloid leukemia (AML) remains a challenge for clinicians. This study aims to construct a novel risk model for AML patient through comprehensive analysis of scRNA and bulk RNA data to optimize the precise treatment strategies for patients and improve prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>scRNA-seq classified cells into nine clusters, including Bcells, erythrocyte, granulocyte-macrophage progenitor (GMP), hematopoietic stem cell progenitors (HSC\/Prog), monocyte\/macrophagocyte (Mono\/Macro), myelocyte, neutrophils, plasma, and T\/NK cells. Functional analysis demonstrated the important role of inflammation immune response in the pathogenesis of AML, and the leukocyte transendothelial migration and adhesion in the process of inflammation should be noticed. ssGSEA method identified four core cells including GMP, HSC\/Prog, Mono\/Macro, and myelocyte for subsequent analysis, which contains 1,594 marker genes. Furthermore, we identified AML-associated genes (2,067genes) and DEGs (1,010genes) between AML patients and controls usingGSE114868dataset. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of five signature genes, namely, CALR, KDM1A, SUCNR1, TMEM220, and ADM. The prognostic model was then validated by two external datasets. Patients with high-risk scores are predisposed to experience poor overall survival. Further GSEA analysis of risk-model-related genes revealed the significant differences in inflammatory response between high-and low-risk groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, we constructed an inflammation related risk model using internal scRNA data and external bulk RNA data, which can accurately distinguish survival outcomes in AML patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1565954","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:22:29Z","timestamp":1749532949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Construction of a novel inflammatory-related prognostic signature of acute myelocytic leukemia based on conjoint analysis of single-cell and bulk RNA sequencing"],"prefix":"10.3389","volume":"16","author":[{"given":"Yongfen","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingbo","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA: A Cancer J Clinicians"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21873","article-title":"Acute myeloid leukemia management and research in 2025","volume":"75","author":"Kantarjian","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26822","article-title":"Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management","volume":"98","author":"Shimony","year":"2023","journal-title":"Am J Hematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01696-w","article-title":"METTL3 mediates chemoresistance by enhancing AML homing and engraftment via ITGA4","volume":"36","author":"Li","year":"2022","journal-title":"Leukemia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01806-0","article-title":"Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery","volume":"27","author":"Bonev","year":"2024","journal-title":"Nat Neurosci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC05700G","article-title":"Time-resolved single-cell transcriptomic sequencing","volume":"15","author":"Xu","year":"2024","journal-title":"Chem Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adp0004","article-title":"BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML","volume":"16","author":"Kumar","year":"2024","journal-title":"Sci Transl Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1186\/s13287-024-03969-w","article-title":"Single-cell dissection reveals promotive role of ENO1 in leukemia stem cell self-renewal and chemoresistance in acute myeloid leukemia","volume":"15","author":"Tian","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s41392-024-02045-2","article-title":"CXCR1(+) neutrophil infiltration orchestrates response to third-generation EGFR-TKI in EGFR mutant non-small-cell lung cancer","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1482361","DOI":"10.3389\/fimmu.2024.1482361","article-title":"Identification of key biomarkers related to fibrocartilage chondrocytes for osteoarthritis based on bulk, single-cell transcriptomic data","volume":"15","author":"Pan","year":"2024","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01789-6","article-title":"Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed\/refractory acute myeloid leukemia","volume":"37","author":"Li","year":"2023","journal-title":"Leukemia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130224","article-title":"Mechanisms of leukocyte transendothelial migration","volume":"6","author":"Muller","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00117-0","article-title":"Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response","volume":"24","author":"Muller","year":"2003","journal-title":"Trends Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: the leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-784116","article-title":"Chronic immune response dysregulation in MDS pathogenesis","volume":"132","author":"Barreyro","year":"2018","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.623952","article-title":"Clinical implications of inflammation in acute myeloid leukemia","volume":"11","author":"Recher","year":"2021","journal-title":"Front Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02136-7","article-title":"Inflammatory recruitment of healthy hematopoietic stem and progenitor cells in the acute myeloid leukemia niche","volume":"38","author":"Chen","year":"2024","journal-title":"Leukemia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s43018-023-00518-x","article-title":"An inflammatory state remodels the immune microenvironment and improves risk stratification in acute myeloid leukemia","volume":"4","author":"Lasry","year":"2023","journal-title":"Nat Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e2310818","DOI":"10.1002\/adma.202310818","article-title":"Bioinspired tumor calcification-guided early diagnosis and eradication of hepatocellular carcinoma","volume":"36","author":"Bai","year":"2024","journal-title":"Adv Mater"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109144118","article-title":"HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt\/beta-catenin pathway activation","volume":"118","author":"Liu","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-019-01532-0","article-title":"Calreticulin in phagocytosis and cancer: opposite roles in immune response outcomes","volume":"24","author":"Schcolnik-Cabrera","year":"2019","journal-title":"Apoptosis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1291720","article-title":"Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma","volume":"13","author":"Chen","year":"2023","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-731737","article-title":"Calreticulin exposure by Malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients","volume":"128","author":"Fucikova","year":"2016","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.234","article-title":"Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition","volume":"29","author":"Lin","year":"2010","journal-title":"Oncogene"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-1739","article-title":"Inhibiting interactions of lysine demethylase LSD1 with snail\/slug blocks cancer cell invasion","volume":"73","author":"Ferrari-Amorotti","year":"2013","journal-title":"Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1016\/j.immuni.2024.09.002","article-title":"The transcription regulators ZNF750 and LSD1\/KDM1A dampen inflammation on the skin's surface by silencing pattern recognition receptors","volume":"57","author":"Liu","year":"2024","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s13045-019-0811-9","article-title":"LSD1\/KDM1A inhibitors in clinical trials: advances and prospects","volume":"12","author":"Fang","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.ccell.2018.02.002","article-title":"ORY-1001, a potent and selective covalent KDM1A inhibitor, for the treatment of acute leukemia","volume":"33","author":"Maes","year":"2018","journal-title":"Cancer Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.cmet.2023.03.004","article-title":"SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression","volume":"35","author":"Villanueva-Carmona","year":"2023","journal-title":"Cell Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0372-7","article-title":"SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity","volume":"20","author":"Keiran","year":"2019","journal-title":"Nat Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-021-00370-0","article-title":"Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma","volume":"29","author":"Li","year":"2022","journal-title":"Cancer Gene Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203179","article-title":"Development and validation of a risk prediction model and nomogram for colon adenocarcinoma based on methylation-driven genes","volume":"13","author":"Zhu","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1002\/mc.23359","article-title":"Prognostic signatures and potential pathogenesis of eRNAs-related genes in colon adenocarcinoma","volume":"61","author":"Rong","year":"2022","journal-title":"Mol Carcinog"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/6.9.811","article-title":"Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium","volume":"6","author":"Nikitenko","year":"2000","journal-title":"Mol Hum Reprod"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.21.2.0396","article-title":"Adrenomedullin, a multifunctional regulatory peptide","volume":"21","author":"Hinson","year":"2000","journal-title":"Endocr Rev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.v215:1","article-title":"Adrenomedullin is anti-apoptotic in osteoblasts through CGRP1 receptors and MEK-ERK pathway","volume":"215","author":"Uzan","year":"2008","journal-title":"J Cell Physiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0167-0115(03)00018-1","article-title":"Adrenomedullin and adrenomedullin binding protein-1 downregulate TNF-alpha in macrophage cell line and rat Kupffer cells","volume":"112","author":"Wu","year":"2003","journal-title":"Regul Pept"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.684396","article-title":"Adrenomedullin expression characterizes leukemia stem cells and associates with an inflammatory signature in acute myeloid leukemia","volume":"11","author":"Simonetti","year":"2021","journal-title":"Front Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01003-x","article-title":"Bone marrow inflammation in haematological Malignancies","volume":"24","author":"de Jong","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI152673","article-title":"Bone marrow-confined IL-6 signaling mediates the progression of myelodysplastic syndromes to acute myeloid leukemia","volume":"132","author":"Mei","year":"2022","journal-title":"J Clin Invest"},{"key":"B41","doi-asserted-by":"publisher","first-page":"20406207241301948","DOI":"10.1177\/20406207241301948","article-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","volume":"15","author":"Zhang","year":"2024","journal-title":"Ther Adv Hematol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017007856","article-title":"Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance","volume":"1","author":"Stevens","year":"2017","journal-title":"Blood Adv"},{"key":"B43","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","article-title":"Interleukin-10 and the interleukin-10 receptor","volume":"19","author":"Moore","year":"2001","journal-title":"Annu Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3535","article-title":"Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages","volume":"356","author":"Ip","year":"2017","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s43556-025-00262-x","article-title":"Indoleamine 2,3-dioxygenase 1 alters the proportions of B cell subpopulations in the microenvironment of acute myeloid leukemia","volume":"6","author":"Yao","year":"2025","journal-title":"Mol Biomed"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01375-2","article-title":"Regulatory T cells promote the stemness of leukemia stem cells through IL10 cytokine-related signaling pathway","volume":"36","author":"Xu","year":"2022","journal-title":"Leukemia"},{"key":"B47","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41408-021-00536-x","article-title":"Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells","volume":"11","author":"Chen","year":"2021","journal-title":"Blood Cancer J"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2023.12.001","article-title":"Inflammatory response signature score model for predicting immunotherapy response and pan-cancer prognosis","volume":"23","author":"Chen","year":"2024","journal-title":"Comput Struct Biotechnol J"},{"key":"B49","doi-asserted-by":"publisher","first-page":"9345","DOI":"10.3390\/ijms25179345","article-title":"A combined proteomic and transcriptomic signature is predictive of response to anti-PD-1 treatment: A retrospective study in metastatic melanoma patients","volume":"25","author":"Mallardo","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12967-023-03971-5","article-title":"IL-6 as new prognostic factor in patients with advanced cutaneous squamous cell carcinoma treated with cemiplimab","volume":"21","author":"Mallardo","year":"2023","journal-title":"J Transl Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1565954\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:22:30Z","timestamp":1749532950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1565954\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2025.1565954"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1565954","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]},"article-number":"1565954"}}