NEAT1 lncRNA overexpression results in short-term progression and poor treatment outcome in childhood B-ALL

Childhood acute lymphoblastic leukaemia (chALL) remains the most prevalent malignancy in children and adolescents. Improving risk stratification and providing personalized prognosis and treatment remain major clinical challenges. Herein, we analysed the clinical utility of NEAT1 lncRNA for the prognosis and prediction of treatment outcome of childhood B-cell precursor ALL (chB-ALL). NEAT1_1 isoform was quantified in bone marrow samples of chB-ALL patients at diagnosis (n = 160) and at the end of induction (n = 108) of ALL-BFM protocol, and in age-matched healthy children (n = 68). Relapse and death served as clinical end-points for survival analysis. Bootstrap analysis was performed for internal validation and decision curve analysis assessed the clinical net benefit for chB-ALL prognosis. Our analysis showed that chB-ALL patients with NEAT1 overexpression at diagnosis are at significantly higher risk for progression (HR = 2.957, 95% CI: 1.122-7.790, p = 0.011) and worse survival (HR = 5.832, 95% CI: 1.259-27.01, p = 0.012), independently of clinicopathological and treatment data. Moreover, NEAT1-fitted multivariate models resulted in improved risk stratification compared to the conventional disease markers of white blood cells, bone marrow response and minimal residual disease, while decision curve analysis highlighted the superior clinical net benefit for chB-ALL prognosis. In conclusion, NEAT1 overexpression constitutes a powerful, independent predictor of poor treatment outcomes and disease progression of chB-ALL, providing refined stratification of patient's risk.