Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

:: is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ::-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62];  = 0.03). In an independent validation cohort of low-risk ::-positive B-cell ALL ( = 68) high expression at diagnosis had an HR = 4.78 [1.07, 21.36] ( = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ::-negative B-cell ALL, high expression at diagnosis had an HR = 3.93 [1.31, 11.79] ( = 0.01). Our results suggest high expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.