Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide

•The EMG mutations were associated with poor prognosis in APL.•Sanz risk system was useful to predict the CR and OS upon ATRA/ATO treatment.

BackgroundAcute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL.MethodsWe included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or -TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2.ResultsMore high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease-free survival in both training (HR = 6.761, 95% CI 2.179–20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089–14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS.ConclusionIn an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL.