High expression of the ETS transcription factor ERG predicts adverse outcome in acute T-lymphoblastic leukemia in adults

Purpose In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL. Patients and Methods ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG's median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR. Results High ERG expressers compared with low ERG expressers had an inferior overall survival ( OS, P =.02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P =.003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression ( P =.005), immunophenotypic subgroups ( early v mature v thymic T-ALL; overall P =.04), HOX11L2 positivity ( P =.055), and absence of HOX11 ( P =.017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL ( n = 57), high ERG ( HR, 4.1; P =.02) and presence of HOX11L2 ( HR, 6.6; P =.008) were independent adverse factors for RFS. Conclusion High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.