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Here, we constructed an AML single-cell transcriptome atlas and proposed sciNMF workflow to systematically dissect underlying cellular heterogeneity. Notably, sciNMF identified 26 leukemic and immune cell states that linked to clinical variables, mutations, and prognosis. By examining the co-existence patterns among these cell states, we highlighted a unique AML cellular ecosystem (ACE) that signifies aberrant tumor milieu and poor survival, which is confirmed by public RNA-seq cohorts. We further developed the ACE signature (ACEsig), comprising 12 genes, which accurately predicts AML prognosis, and outperforms existing signatures. When applied to cytogenetically normal AML or intensively treated patients, the ACEsig continues to demonstrate strong performance. Our results demonstrate that large-scale systematic characterization of cellular heterogeneity has the potential to enhance our understanding of AML heterogeneity and contribute to more precise risk stratification strategy.<\/jats:p>","DOI":"10.1093\/bib\/bbaf028","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T04:17:56Z","timestamp":1736569076000},"source":"Crossref","is-referenced-by-count":2,"title":["Deciphering cell states and the cellular ecosystem to improve risk stratification in acute myeloid leukemia"],"prefix":"10.1093","volume":"26","author":[{"given":"Zheyang","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]},{"name":"National Institute for Data Science in Health and Medicine, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghan","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Medical University Union Hospital , No. 29 Xinquan Street, Gulou District, Fuzhou 350001 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Medical University Union Hospital , No. 29 Xinquan Street, Gulou District, Fuzhou 350001 ,","place":["China"]},{"name":"Department of Hematology and Rheumatology, The Second Affiliated Hospital of Xiamen Medical College , No. 566 Shengguang Road, Jimei District, Xiamen 361021 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengsha","family":"Tong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]},{"name":"National Institute for Data Science in Health and Medicine, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nainong","family":"Li","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Center, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Department of Hematology, Fujian Medical University Union Hospital , No. 29 Xinquan Street, Gulou District, Fuzhou 350001 ,","place":["China"]},{"name":"Translational Medicine Center on Hematology, Fujian Medical University , No. 29 Xinquan Street, Gulou District, Fuzhou 350001 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-1144","authenticated-orcid":false,"given":"Jialiang","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, Xiang\u2019an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 ,","place":["China"]},{"name":"National Institute for Data Science in Health and Medicine, Xiamen University , No. 4221, Xiang\u2019an South Road, Xiamen, Fujian 361102 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