{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:00:03Z","timestamp":1775113203185,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":50,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The project was funded by the Yunnan Province Clinical Research Center for Hematologic Disease","award":["2023YJZX-XY02"],"award-info":[{"award-number":["2023YJZX-XY02"]}]},{"name":"the Kunming University of Science and Technology & the First People's Hospital of Yunnan Province Joint Special Project on Medical Research","award":["KUST-KH2022028Y"],"award-info":[{"award-number":["KUST-KH2022028Y"]}]},{"name":"Yunnan Fundamental Research Projects","award":["202401AY070001-109"],"award-info":[{"award-number":["202401AY070001-109"]}]},{"name":"Major projects of Yunnan Province","award":["202403AC100017"],"award-info":[{"award-number":["202403AC100017"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-025-04215-2","type":"journal-article","created":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T09:36:22Z","timestamp":1765100182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting immunotherapeutic response and therapeutic targets by stemness classification of acute myeloid leukemia by stemness score"],"prefix":"10.1007","volume":"17","author":[{"given":"Xin","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuzhen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujing","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"issue":"11","key":"4215_CR1","doi-asserted-by":"publisher","first-page":"4375","DOI":"10.1007\/s00277-024-05963-x","volume":"103","author":"SK Prajapati","year":"2024","unstructured":"Prajapati SK, Kumari N, Bhowmik D, Gupta R. Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia. Ann Hematol. 2024;103(11):4375\u2013400.","journal-title":"Ann Hematol"},{"issue":"23","key":"4215_CR2","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"9","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. The New Engl J Med Jun. 2016;9(23):2209\u201321.","journal-title":"The New Engl J Med Jun"},{"issue":"2","key":"4215_CR3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.stem.2018.01.011","volume":"1","author":"RL Bowman","year":"2018","unstructured":"Bowman RL, Busque L, Levine RL. Clonal hematopoiesis and evolution to hematopoietic malignancies. Cell Stem Cell Feb. 2018;1(2):157\u201370.","journal-title":"Cell Stem Cell Feb"},{"issue":"2","key":"4215_CR4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1182\/blood.2019001239","volume":"9","author":"CD DiNardo","year":"2020","unstructured":"DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood Jan. 2020;9(2):85\u201396.","journal-title":"Blood Jan"},{"issue":"8","key":"4215_CR5","first-page":"7293","volume":"23","author":"Y Wang","year":"2024","unstructured":"Wang Y, Han Y, Jin L, et al. A novel prognostic signature based on cancer stemness and metabolism-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma. Aging Apr. 2024;23(8):7293\u2013310.","journal-title":"Aging Apr"},{"key":"4215_CR6","doi-asserted-by":"publisher","first-page":"775128","DOI":"10.3389\/fimmu.2021.775128","volume":"12","author":"T Marchand","year":"2021","unstructured":"Marchand T, Pinho S. Leukemic stem cells: from leukemic niche biology to treatment opportunities. Front Immunol. 2021;12:775128.","journal-title":"Front Immunol"},{"issue":"20","key":"4215_CR7","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1080\/15384101.2020.1810402","volume":"19","author":"CH Nguyen","year":"2020","unstructured":"Nguyen CH, Grandits AM, Purton LE, Sill H, Wieser R. All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. Cell cycle (Georgetown, Tex). 2020;19(20):2573\u201388.","journal-title":"Cell cycle (Georgetown, Tex.)"},{"key":"4215_CR8","doi-asserted-by":"publisher","first-page":"1202825","DOI":"10.3389\/fimmu.2023.1202825","volume":"14","author":"Y Huang","year":"2023","unstructured":"Huang Y, Zhang Z, Sui M, et al. A novel stemness classification in acute myeloid leukemia by the stemness index and the identification of cancer stem cell-related biomarkers. Front Immunol. 2023;14:1202825.","journal-title":"Front Immunol"},{"issue":"2","key":"4215_CR9","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1159\/000536152","volume":"147","author":"F Wachter","year":"2024","unstructured":"Wachter F, Pikman Y. Pathophysiology of acute myeloid leukemia. Acta Haematol. 2024;147(2):229\u201346.","journal-title":"Acta Haematol"},{"issue":"6","key":"4215_CR10","doi-asserted-by":"publisher","first-page":"974","DOI":"10.3724\/abbs.2023101","volume":"2","author":"X Mu","year":"2023","unstructured":"Mu X, Chen C, Dong L, et al. Immunotherapy in leukaemia. Acta Biochim Et Biophys Sinica Jun. 2023;2(6):974\u201387.","journal-title":"Acta Biochim Et Biophys Sinica Jun"},{"issue":"11","key":"4215_CR11","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1021\/acs.accounts.0c00339","volume":"53","author":"X Han","year":"2020","unstructured":"Han X, Li H, Zhou D, Chen Z, Gu Z. Local and targeted delivery of immune checkpoint blockade therapeutics. Acc Chem Res. 2020;53(11):2521\u201333.","journal-title":"Acc Chem Res"},{"key":"4215_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116132","volume":"171","author":"Y Wu","year":"2024","unstructured":"Wu Y, Li Y, Gao Y, et al. Immunotherapies of acute myeloid leukemia: rationale, clinical evidence and perspective. Biomed Pharmacother. 2024;171:116132.","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"4215_CR13","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.3390\/biomedicines11061724","volume":"15","author":"D Damiani","year":"2023","unstructured":"Damiani D, Tiribelli M. Checkpoint Inhibitors in Acute Myeloid Leukemia. Biomedicines Jun. 2023;15(6):1724.","journal-title":"Biomedicines Jun"},{"issue":"7633","key":"4215_CR14","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/nature20598","volume":"15","author":"SW Ng","year":"2016","unstructured":"Ng SW, Mitchell A, Kennedy JA, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature Dec. 2016;15(7633):433\u20137.","journal-title":"Nature Dec"},{"key":"4215_CR15","doi-asserted-by":"publisher","first-page":"1168780","DOI":"10.3389\/fimmu.2023.1168780","volume":"14","author":"J Zhou","year":"2023","unstructured":"Zhou J, Huang J, Li Z, et al. Identification of aging-related biomarkers and immune infiltration characteristics in osteoarthritis based on bioinformatics analysis and machine learning. Front Immunol. 2023;14:1168780.","journal-title":"Front Immunol"},{"issue":"1","key":"4215_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83913-7","volume":"11","author":"KE Craven","year":"2021","unstructured":"Craven KE, G\u00f6kmen-Polar Y, Badve SS. CIBERSORT analysis of TCGA and METABRIC identifies subgroups with better outcomes in triple negative breast cancer. Sci Rep. 2021;11(1):4691.","journal-title":"Sci Rep"},{"issue":"23","key":"4215_CR17","doi-asserted-by":"publisher","first-page":"6575","DOI":"10.1158\/0008-5472.CAN-18-0689","volume":"1","author":"L Xu","year":"2018","unstructured":"Xu L, Deng C, Pang B, et al. TIP: A web server for resolving tumor immunophenotype profiling. Cancer Res Dec. 2018;1(23):6575\u201380.","journal-title":"Cancer Res Dec"},{"issue":"2","key":"4215_CR18","first-page":"741","volume":"28","author":"J Liu","year":"2019","unstructured":"Liu J, Ge Y, Wu S, et al. Association between antidiabetic agents use and leukocyte telomere shortening rates in patients with type 2 diabetes. Aging (Albany NY) Jan. 2019;28(2):741\u201355.","journal-title":"Aging (Albany NY) Jan"},{"issue":"8","key":"4215_CR19","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.3390\/ijms21082907","volume":"21","author":"I Nepstad","year":"2020","unstructured":"Nepstad I, Hatfield KJ, Gr\u00f8nnings\u00e6ter IS, Reikvam H. The PI3K-Akt-mTOR signaling pathway in human acute myeloid leukemia (AML) cells. Int J Mol Sci. 2020;21(8):2907.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"4215_CR20","first-page":"178","volume":"11","author":"S Taghiloo","year":"2022","unstructured":"Taghiloo S, Norozi S, Asgarian-Omran H. The effects of PI3K\/Akt\/mTOR signaling pathway inhibitors on the expression of immune checkpoint ligands in acute myeloid leukemia cell line. Iran J Allergy Asthma Immunol Apr. 2022;11(2):178\u201388.","journal-title":"Iran J Allergy Asthma Immunol Apr"},{"issue":"1","key":"4215_CR21","doi-asserted-by":"publisher","first-page":"11444","DOI":"10.1038\/s41598-022-15020-0","volume":"6","author":"F Wang","year":"2022","unstructured":"Wang F, Yang L, Xiao M, et al. PD-L1 regulates cell proliferation and apoptosis in acute myeloid leukemia by activating PI3K-AKT signaling pathway. Scientific Rep Jul. 2022;6(1):11444.","journal-title":"Scientific Rep Jul"},{"issue":"19","key":"4215_CR22","first-page":"1965","volume":"9","author":"H Gu","year":"2024","unstructured":"Gu H, Chen C, Hou ZS, et al. PI3K\u03b3 maintains the self-renewal of acute myeloid leukemia stem cells by regulating the Pentose phosphate pathway. May. 2024;9(19):1965\u201379.","journal-title":"May"},{"key":"4215_CR23","doi-asserted-by":"publisher","first-page":"101046","DOI":"10.1016\/j.neo.2024.101046","volume":"57","author":"DS Chandrashekar","year":"2024","unstructured":"Chandrashekar DS, Afaq F, Karthikeyan SK, et al. Bromodomain inhibitor treatment leads to overexpression of multiple kinases in cancer cells. Neoplasia Nov. 2024;57:101046.","journal-title":"Neoplasia Nov"},{"issue":"8","key":"4215_CR24","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1007\/s00109-020-01944-5","volume":"98","author":"A Kirtonia","year":"2020","unstructured":"Kirtonia A, Pandya G, Sethi G, Pandey AK, Das BC, Garg M. A comprehensive review of genetic alterations and molecular targeted therapies for the implementation of personalized medicine in acute myeloid leukemia. J Mol Med (Berl) Aug. 2020;98(8):1069\u201391.","journal-title":"J Mol Med (Berl) Aug"},{"issue":"12","key":"4215_CR25","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1016\/j.ccell.2023.11.001","volume":"11","author":"L Nicosia","year":"2023","unstructured":"Nicosia L, Spencer GJ, Brooks N, et al. Therapeutic targeting of EP300\/CBP by bromodomain Inhibition in hematologic malignancies. Cancer Cell Dec. 2023;11(12):2136\u2013e21532113.","journal-title":"Cancer Cell Dec"},{"issue":"8","key":"4215_CR26","first-page":"671","volume":"2","author":"M Zhong","year":"2022","unstructured":"Zhong M, Gao R, Zhao R, Huang Y, Chen C. BET bromodomain inhibition rescues PD-1-mediated T-cell exhaustion in acute myeloid leukemia. Aug. 2022;2(8):671.","journal-title":"Aug"},{"key":"4215_CR27","doi-asserted-by":"publisher","first-page":"1212476","DOI":"10.3389\/fimmu.2023.1212476","volume":"14","author":"R Rui","year":"2023","unstructured":"Rui R, Zhou L, He S. Cancer immunotherapies: advances and bottlenecks. Front Immunol. 2023;14:1212476.","journal-title":"Front Immunol"},{"issue":"3","key":"4215_CR28","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1001\/jamaoncol.2019.5367","volume":"1","author":"J Duan","year":"2020","unstructured":"Duan J, Cui L, Zhao X, et al. Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer: A systematic review and Meta-analysis. JAMA Oncol Mar. 2020;1(3):375\u201384.","journal-title":"JAMA Oncol Mar"},{"issue":"20","key":"4215_CR29","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.3390\/cancers16203443","volume":"10","author":"J Greiner","year":"2024","unstructured":"Greiner J, Mohamed E, Fletcher DM. Immunotherapeutic potential of mutated npm1 for the treatment of acute myeloid leukemia. Cancers. 2024;10(20):3443.","journal-title":"Cancers"},{"issue":"9","key":"4215_CR30","first-page":"1470","volume":"1","author":"P Williams","year":"2019","unstructured":"Williams P, Basu S, Garcia-Manero G, et al. The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia. May. 2019;1(9):1470\u201381.","journal-title":"May"},{"issue":"1","key":"4215_CR31","first-page":"28","volume":"3","author":"C Chen","year":"2020","unstructured":"Chen C, Liang C, Wang S, Chio CL, Zhang Y, Zeng C. Expression patterns of immune checkpoints in acute myeloid leukemia. Apr. 2020;3(1):28.","journal-title":"Apr"},{"issue":"4","key":"4215_CR32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11912-019-0781-7","volume":"23","author":"M Stahl","year":"2019","unstructured":"Stahl M, Goldberg AD. Immune checkpoint inhibitors in acute myeloid leukemia: novel combinations and therapeutic targets. Curr Oncol Rep Mar. 2019;23(4):37.","journal-title":"Curr Oncol Rep Mar"},{"key":"4215_CR33","doi-asserted-by":"publisher","first-page":"4541571","DOI":"10.1155\/2022\/4541571","volume":"2022","author":"Y Yue","year":"2022","unstructured":"Yue Y, Wu Y. Pan-cancer analysis predicts the immunological and prognostic role of zc3H12C in KIRC. Biomed Res Int. 2022;2022:4541571.","journal-title":"Biomed Res Int"},{"key":"4215_CR34","doi-asserted-by":"publisher","first-page":"104837","DOI":"10.1016\/j.cellimm.2024.104837","volume":"401","author":"Y Zhao","year":"2024","unstructured":"Zhao Y, Zhu M, Wu S, et al. Unlocking the power of Zc3h12c: orchestrating macrophage activation and elevating the innate immune response. Cell Immunol 2024;401:104837.","journal-title":"Cell Immunol\u00a0"},{"issue":"1","key":"4215_CR35","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13062-025-00666-3","volume":"22","author":"V Longo","year":"2025","unstructured":"Longo V, Mazzone P, Calice G, et al. CLIC2 regulates immunosuppression and macrophage differentiation in genomically stable gastric cancer. Biol Direct Jul. 2025;22(1):89.","journal-title":"Biol Direct Jul"},{"issue":"12","key":"4215_CR36","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.32604\/or.2024.055286","volume":"32","author":"Z Wang","year":"2024","unstructured":"Wang Z, Fu J, Zhu S, et al. Identification of M2 macrophage-related genes for establishing a prognostic model in pancreatic cancer: FCGR3A as key gene. Oncol Res. 2024;32(12):1851\u201366.","journal-title":"Oncol Res"},{"key":"4215_CR37","doi-asserted-by":"publisher","first-page":"102664","DOI":"10.1016\/j.ebiom.2020.102664","volume":"52","author":"Y Fu","year":"2020","unstructured":"Fu Y, Xu M, Cui Z, et al. Genome-wide identification of FHL1 as a powerful prognostic candidate and potential therapeutic target in acute myeloid leukaemia. EBioMedicine Feb. 2020;52:102664.","journal-title":"EBioMedicine Feb"},{"issue":"33","key":"4215_CR38","doi-asserted-by":"publisher","first-page":"13560","DOI":"10.1523\/JNEUROSCI.0321-13.2013","volume":"14","author":"SM Glasgow","year":"2013","unstructured":"Glasgow SM, Laug D, Brawley VS, et al. The miR-223\/nuclear factor I-A axis regulates glial precursor proliferation and tumorigenesis in the CNS. J Neurosci Aug. 2013;14(33):13560\u20138.","journal-title":"J Neurosci Aug"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-04215-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-025-04215-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-04215-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:35:29Z","timestamp":1775111729000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-025-04215-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,7]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4215"],"URL":"https:\/\/doi.org\/10.1007\/s12672-025-04215-2","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,7]]},"assertion":[{"value":"17 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article has been updated to correct the affiliation of author Yu Zhang.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to\u00a0participate"}},{"value":"All authors consent to publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"157"}}