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Herein we performed a prospective study on clinical significance of flow cytometry\u2010based pSTAT5 in adult B\u2010ALL patients. A total of 184 patients were enrolled in the Precision\u2010Classification\u2010Directed\u2010Target\u2010Total\u2010Therapy (PDT)\u2010ALL\u20102016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow\u2010pSTAT5, the population was classified into pSTAT5<jats:sup>low<\/jats:sup> (113\/184, 61.1%) and pSTAT5<jats:sup>high<\/jats:sup> (71\/184, 38.9%). Overall survival (OS) and event\u2010free survival (EFS) were inferior in pSTAT5<jats:sup>high<\/jats:sup> patients than in those with pSTAT5<jats:sup>low<\/jats:sup> (OS, 44.8% vs. 65.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.004; EFS, 23.5% vs. 52.1%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow\u2010based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5<jats:sup>high<\/jats:sup>\u2009+\u2009MRD+), standard risk (SR, pSTAT5<jats:sup>low<\/jats:sup>\u2009+\u2009MRD\u2212) and others as moderate\u2010risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3\u2010year OS rates, 36.5%, 56.7% and 76.3%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), which was confirmed on multivariate analysis (hazard ratio 3.53, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Collectively, our study proposed a novel, simple and flow\u2010based risk classification by integrating pSTAT5 and MRD in favour of risk\u2010guided treatment for B\u2010ALL.<\/jats:p>","DOI":"10.1111\/bjh.19467","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T09:37:10Z","timestamp":1713519430000},"page":"517-528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>STAT5<\/scp> phosphorylation plus minimal residual disease defines a novel risk classification in adult B\u2010cell acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9675-1740","authenticated-orcid":false,"given":"Xiuli","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Department of Hematology Ganzhou People's Hospital (Nanfang Hospital Ganzhou 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