STAT5 phosphorylation plus minimal residual disease defines a novel risk classification in adult B‐cell acute lymphoblastic leukaemia

Abstract

SummaryThe dysregulation of the Janus family tyrosine kinase‐signal transducer and activator of transcription (JAK‐STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry‐based pSTAT5 in adult B‐ALL patients. A total of 184 patients were enrolled in the Precision‐Classification‐Directed‐Target‐Total‐Therapy (PDT)‐ALL‐2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow‐pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event‐free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow‐based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD−) and others as moderate‐risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3‐year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow‐based risk classification by integrating pSTAT5 and MRD in favour of risk‐guided treatment for B‐ALL.