Genetic basis of pediatric T-cell acute lymphoblastic leukemia and its clinical impact

Abstract

Despite an improvement in the prognosis of pediatric T-cell acute lymphoblastic leukemia (T-ALL), the outcome of patients with relapse or refractory T-ALL remains dismal. Activating mutations of the NOTCH pathway and the loss-of-function mutations of CDKN2A are frequent genetic alterations in T-ALL; however, these changes exert no prognostic impact. Furthermore, several gene fusions, including STIL-TAL1, were recently detected in T-ALL; however, other genetic events are necessary for the development of T-ALL. Recently, we detected novel recurrent SPI1 fusions in T-ALL by RNA sequencing using next-generation sequencing technology. Patients with SPI1 fusions revealed highly poor prognosis, suggesting that these fusions would be useful prognostic markers in T-ALL. Furthermore, the intensification of treatment of patients with SPI1 fusions may contribute to the improvement of the outcome of patients with T-ALL.