{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:56:27Z","timestamp":1790679387248,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70115443"],"award-info":[{"award-number":["70115443"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["413490537"],"award-info":[{"award-number":["413490537"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005677","name":"Jos\u00e9 Carreras Leuk\u00e4mie-Stiftung","doi-asserted-by":"publisher","award":["DJCLS 08R\/2024"],"award-info":[{"award-number":["DJCLS 08R\/2024"]}],"id":[{"id":"10.13039\/501100005677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) comprises molecularly diverse subtypes, but robust cross\u2010cohort validations and operational gene\u2010expression definitions are lacking. To establish a gene\u2010expression\u2013anchored framework for T\u2010ALL subtyping, we aggregated 2314 transcriptomes (15 cohorts, age: 0.8\u201390.8 years). An extended unsupervised approach defined 17 main clusters and 3 subclusters in samples with high blast fractions. Supervised analyses added an overarching immature T\u2010ALL (early T cell precursor [ETP]\u2010like) definition and resolved the LMO2 \u03b3\u03b4\u2010like subtype. All clusters contained samples from at least two cohorts. Characteristic genomic driver enrichments were consistent across cohorts, while gene\u2010expression clusters did not correspond exclusively to single driver events but also reflected developmental origins. A machine\u2010learning classifier based on ALLCatchR, our B\u2010cell acute lymphoblastic leukemia (B\u2010ALL) classifier, identified these 20 transcriptomic subtypes and the immature T\u2010ALL (ETP\u2010like) signature with 0.995\u20131.0 accuracy in a validation set (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009203). Testing the classifier on a second hold\u2010out data set (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009265 samples) showed that 92.7% of predictions matched with corresponding driver alterations. Across all samples, 83.2% of cases received high\u2010confidence predictions, 7.3% candidate predictions, and 9.5% remained unclassified, largely because of low blast fractions. We identified a novel gene\u2010expression cluster markedly enriched (P\u2009&lt;\u20090.001) for clonal hematopoiesis mutations (\n                    <jats:italic>IDH2 R140Q<\/jats:italic>\n                    ,\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    ) and a stem\u2010\/progenitor cell\u2010like gene expression. This novel clonal hematopoiesis\u2010related T\u2010ALL subtype was observed in six cohorts and accounted for 8.9% of adults and 39.5% of patients aged &gt;50 years. We extended\u00a0ALLCatchR into ALLCatchR2, a free R package that now enables B\u2010\/T\u2010lineage separation, gene\u2010expression subtyping, blast estimation, and developmental annotation to harmonize T\u2010ALL classification across studies and clinical contexts.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70475","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:47:48Z","timestamp":1789400868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The machine\u2010learning classifier ALLCatchR2 identifies 20 T\u2010ALL subtypes across cohorts and age groups"],"prefix":"10.1002","volume":"10","author":[{"given":"Thomas","family":"Beder","sequence":"first","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Wolgast","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-9838","authenticated-orcid":false,"given":"Wencke","family":"Walter","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0644-9140","authenticated-orcid":false,"given":"Sonja","family":"Bendig","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0638-0000","authenticated-orcid":false,"given":"Alina M.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwine J.","family":"Barz","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-7124","authenticated-orcid":false,"given":"Marketa","family":"Zaliova","sequence":"additional","affiliation":[{"name":"Childhood Leukaemia Investigation Prague, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa\u2010Sophie","family":"Reitzel","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4519-1002","authenticated-orcid":false,"given":"David","family":"Baden","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Cancer Immunology (Campus Benjamin Franklin) Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t and Humboldt\u2010Universit\u00e4t zu Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"G\u00f6kbuget","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Hematology\/Oncology Goethe University Frankfurt, University Hospital Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart","family":"Kester","sequence":"additional","affiliation":[{"name":"Princess Maxima Center for Pediatric Oncology Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Trka","sequence":"additional","affiliation":[{"name":"Childhood Leukaemia Investigation Prague, Second Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Haferlach","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia D.","family":"Baldus","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Neumann","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-9437","authenticated-orcid":false,"given":"Lorenz","family":"Bastian","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Hospital Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit \u201cCATCH ALL\u201d (KFO 5010) Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00018-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-3900"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.02.008"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3909"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2120787119"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01743-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02264-0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01620-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07807-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010385"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11796"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717125115"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.190587"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0037-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002337"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130189"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.21.00326"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2022.08.001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00479-5"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgae011"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70366"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqaa078"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000939"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021752"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025031402"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025031466"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00863-5"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024027270"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808253"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0315-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022920"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2025-336"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-23-0106"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01068-4"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lrr.2023.100408"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19250"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70475","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hem3.70475","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.70475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:36Z","timestamp":1790676636000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.70475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/hem3.70475"],"URL":"https:\/\/doi.org\/10.1002\/hem3.70475","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70475"}}