High EVI 1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group

Summary Ectopic viral integration site‐1 ( EVI 1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia ( AML ), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI 1 high , defined as expression in excess of normal controls, in paediatric AML . EVI 1 m RNA expression was measured via quantitative real‐time polymerase chain reaction in diagnostic specimens obtained from 206 patients. Expression levels were correlated with clinical features and outcome. EVI 1 high was present in 58/206 (28%) patients. MLL rearrangements occurred in 40% of EVI 1 high patients as opposed to 12% of the EVI 1 low/absent patients ( P  < 0·001). No abnormalities of 3q26 were found in EVI 1 high patients by conventional cytogenetic analysis, nor were cryptic 3q26 abnormalities detected in a subset of patients screened by next‐generation sequencing. French‐American‐British class M7 was enriched in the EVI 1 high group, accounting for 24% of these patients. EVI 1 high patients had significantly lower 5‐year overall survival from study entry (51% vs. 68%, P  = 0·015). However, in multivariate analysis including other established prognostic markers, EVI 1 expression did not retain independent prognostic significance. EVI 1 expression is currently being studied in a larger cohort of patients enrolled on subsequent Children's Oncology Group trials, to determine if EVI 1 high has prognostic value in MLL ‐ rearranged or intermediate‐risk subsets.