{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:46:21Z","timestamp":1790318781228,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270190"],"award-info":[{"award-number":["82270190"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300267"],"award-info":[{"award-number":["82300267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC0840605"],"award-info":[{"award-number":["2019YFC0840605"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) is a highly heterogeneous disease with a challenging prognosis, particularly in adult patients. We enrolled 88 adult B\u2010ALL patients with transcriptomic and mutation profiles for classification system identification, and a comprehensive system for B\u2010ALL patients (COMBAT) was developed. COMBAT stratified patients into three cohorts: (1) COMBAT1, characterized by high stem\/myeloid antigen expression, low immune infiltration, high infiltration of endothelial cells, and hypo\u2010CIMP (CpG island methylator phenotype); (2) COMBAT2, defined as an inflamed subtype with immune exhaustion, moderate myeloid antigen expression, and hypo\u2010CIMP; and (3) COMBAT3, marked by proliferative profiles with MYC pathway activation and hypomethylation at enhancer regions in patients characterized by CIMP. The molecular features of the three COMBATs were verified in two external cohorts, the\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE34861\">GSE34861<\/jats:ext-link>\n                    (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009194) and\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE66005\">GSE66005<\/jats:ext-link>\n                    (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009109) datasets. In univariate analysis, only COMBAT classification presented significance for OS, and patients of COMBAT3 presented significantly superior survival than COMBAT1\/2 in Ph\u2010negative ALL. Ph\u2010negative ALL patients undergoing allogeneic hematopoietic stem cell transplantation (allo\u2010HSCT) in the COMBAT3 group showed better overall survival (OS) than those in the COMBAT1\u20102 groups (estimated 3\u2010year OS: 100% vs. 65.6%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.034), suggesting a prognostic benefit of this subtype. In summary, the COMBAT system redefines the characteristics of adult B\u2010ALL subtypes and guides the selection of allo\u2010HSCT for Ph\u2010negative patients.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70053","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T13:02:16Z","timestamp":1747659736000},"page":"3578-3595","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive omics\u2010based classification system in adult patients with B\u2010cell acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-4184","authenticated-orcid":false,"given":"Yang","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5738-2322","authenticated-orcid":false,"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qishan","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyun","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical 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