Genetic mutational profiling analysis of T cell acute lymphoblastic leukemia reveal mutant FBXW7 as a prognostic indicator for inferior survival
Abstract
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplasm for which there are currently no adequate biomarkers for developing risk-adapted therapeutic regimens to improve the treatment outcome. In this prospective study of 83 Chinese patients (54 children and 29 adults) with de novo T-ALL, we analyzed mutations in 11 T-ALL genes: NOTCH1, FBXW7, PHF6, PTEN, N-RAS, K-RAS, WT1, IL7R, PIK3CA, PIK3RA, and AKT1. NOTCH1 mutations were identified in 51.9 and 37.9 % of pediatric and adult patients, respectively, and these patients showed improved overall survival (OS) and event-free survival (EFS). The FBXW7 mutant was present in 25.9 and 6.9 % of pediatric and adult patients, respectively, and was associated with inferior OS and EFS in pediatric T-ALL. Multivariate analysis revealed that mutant FBXW7 was an independent prognostic indicator for inferior EFS (hazard ratio [HR] 4.38; 95 % confidence interval [CI] 1.15-16.71; p = 0.03) and tended to be associated with reduced OS (HR 2.81; 95 % CI 0.91-8.69; p = 0.074) in pediatric T-ALL. Mutant PHF6 was present in 13 and 20.7 % of our childhood and adult cohorts, respectively, while PTEN mutations were noted in 11.1 % of the pediatric patients. PTEN and NOTCH1 mutations were al...Continue Reading
References
Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia: analysis in adults and children
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