{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T17:31:41Z","timestamp":1786383101041,"version":"build-2736575974"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>PAX5-altered acute lymphoblastic leukemia (PAX5-alt ALL) is a recently recognized molecular subtype of B-ALL characterized by a distinct transcriptional signature and frequent PAX5 fusions (PAX5-r). While PAX5-alt ALL has been associated with intermediate outcomes, clinical data specifically investigating pediatric PAX5-r ALL remain limited. We collected and analyzed 159 pediatric cases of PAX5-r ALL treated between 2001-2024 within AIEOP-BFM ALL studies across Italy, Germany and Austria, revealing high-risk clinical features. Comparative analyses of patients consecutively enrolled in the AIEOP-BFM ALL 2017 study (PAX5-r, n=96 vs. non-PAX5-r, n=1948) confirmed higher rates of hyperleukocytosis at diagnosis (22.9% vs. 8%, p&amp;lt;0.001) and enrichment of IKZF1plus profile (14.7% vs. 7.8%, p=0.0015) in PAX5-r patients. No relevant differences in terms of minimal\/measurable residual disease (MRD)-based treatment response and risk-group stratification were observed. PAX5-r patients had a 4-year EFS and OS of 72.6\u00b15.7% and 95.4\u00b12.3%, respectively. Four-year EFS were 100%, 63.4\u00b19.7% and 63.3\u00b110% for standard-risk, medium-risk (MR) and high-risk (HR) groups, respectively, indicating that the poor prognostic impact of PAX5-r applies only when end-of-induction MRD is positive (MR\/HR). Whole transcriptome sequencing revealed high FLT3 median expression in PAX5-r ALL and high-throughput drug screening of patient-derived xenografts (PDXs) showed marked sensitivity to several FLT3 inhibitors. Gilteritinib showed potent ex vivo cytotoxicity and synergism with dexamethasone in PAX5-r PDX models. Collectively, this study investigated clinical and biological features of pediatric PAX5-r ALL highlighting its MRD-dependent unfavorable prognosis and identifying FLT3 overexpression as a novel, potential therapeutic target.<\/jats:p>","DOI":"10.1182\/blood.2026033546","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T17:10:23Z","timestamp":1786381823000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Measurable Residual Disease-Dependent Unfavorable Outcomes in Pediatric PAX5-Rearranged B-Acute Lymphoblastic Leukemia"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9779-4165","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Peccatori","sequence":"first","affiliation":[{"name":"Tettamanti Center, Fondazione IRCCS San Gerardo Dei Tintori, Monza, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-541X","authenticated-orcid":false,"given":"Karin","family":"Nebral","sequence":"additional","affiliation":[{"name":"Labdia Labordiagnostik GmbH; CCRI, Children's Cancer Research Institute, St. Anna Kinderkrebsforschung;, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-2725","authenticated-orcid":false,"given":"Anke Katharina","family":"Bergmann","sequence":"additional","affiliation":[{"name":"University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-0628","authenticated-orcid":false,"given":"Sabine","family":"Strehl","sequence":"additional","affiliation":[{"name":"St. Anna Children's Cancer Research Institute (CCRI), Vienna, 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