{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:46:46Z","timestamp":1782222406197,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KMT2A<\/jats:italic>\n                    \u2010rearranged B\u2010cell acute lymphoblastic leukemia (\n                    <jats:italic>KMT2A<\/jats:italic>\n                    r B\u2010ALL) exhibits significant heterogeneity in age of onset, developmental origins, and clinical outcomes. The interplay of individual factors influencing early treatment response within this high\u2010risk molecular subtype remains poorly elucidated. To identify determinants of early treatment response to induction chemotherapy, we analyzed 465\n                    <jats:italic>KMT2A<\/jats:italic>\n                    r B\u2010ALL cases spanning a wide age range (1 month to 89 years) by integrating transcriptomic and genomic profiling with functional drug response and measurable residual disease (MRD) kinetics. We observed a strong inverse correlation between MRD clearance with advancing age (P\u2009=\u20092.1E\u221204), proximity to early B\u2010cell\u2010precursor developmental state (low maturity score, P\u2009=\u20091.3E\u221203), and\n                    <jats:italic>AFF1<\/jats:italic>\n                    as fusion partner (P\u2009=\u20097.0E\u221204). A multivariable analysis confirmed the strong impact of maturity (P\u2009=\u20090.02) and\n                    <jats:italic>KMT2A<\/jats:italic>\n                    fusion partner (P\u2009=\u20090.03) on MRD clearance, supporting the concept that the cell's developmental state defines therapy response. Gene expression analysis identified cellular traits that relate to MRD clearance (e.g., chromatin organization, immune modulation, and proliferation). This gene expression classifier grouped cases not only by MRD clearance but also by ex vivo sensitivity to induction therapy drugs. Notably, good responders to ex vivo induction drugs were characterized by a higher maturity score (P\u2009=\u20091.8E\u221203), whereas for less mature\n                    <jats:italic>KMT2A<\/jats:italic>\n                    r B\u2010ALL cases, response profiles suggested higher Venetoclax sensitivity. Our study provides an integrative framework linking developmental phenotype, fusion partner, and MRD kinetics across the full age spectrum of\n                    <jats:italic>KMT2A<\/jats:italic>\n                    r B\u2010ALL. These insights may support future risk\u2010adapted strategies and therapeutic targeting, particularly in immature\n                    <jats:italic>KMT2A<\/jats:italic>\n                    r B\u2010ALL.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70324","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:36:45Z","timestamp":1771511805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intra\u2010subtype heterogeneity shapes treatment response in\n                    <i>KMT2A<\/i>\n                    \u2010rearranged ALL across all age groups"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0638-0000","authenticated-orcid":false,"given":"Alina M.","family":"Hartmann","sequence":"first","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit CATCH ALL 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 Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit CATCH ALL 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 Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit CATCH ALL KFO 5010 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Haas","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology and Children's Research Center University Children's Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Amelunxen","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ehm","sequence":"additional","affiliation":[{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel 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Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Beder","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8795-2212","authenticated-orcid":false,"given":"Fabio D.","family":"Steffen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology and Children's Research Center University Children's Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Rauwolf","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology and Children's Research Center University Children's Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Wolgast","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit CATCH ALL KFO 5010 Kiel 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 Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"},{"name":"Clinical Research Unit CATCH ALL KFO 5010 Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bozzetti","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology and Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel Germany"},{"name":"University Cancer Center Schleswig\u2010Holstein (UCCSH) University Medical Center Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Alten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Pediatric Hematology\/Oncology University Medical Center Schleswig\u2010Holstein, Campus Kiel Kiel 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