Impact of ETV6 mutations on clinical outcomes in acute myeloid leukemia: a real-world retrospective cohort study

As a member of the ETS family, ETV6 has been demonstrated to be implicated with the molecular etiology of various hematopoietic diseases. However, the clinical impact of ETV6 mutations (ETV6mut) in acute myeloid leukemia (AML) remains unclear. Hereon, we included 879 consecutive newly diagnosed AML patients in our institution to elucidate the prognostic impact of ETV6 mutation status. In the overall cohort, ETV6mut were found in 24 cases (2.7%) and were associated with lower hemoglobin levels. The predominant common mutation types were missense mutations (15/31, 48.4%) and frameshift mutations (14/31, 45.2%). ETV6 mutations often occurred in conjunction with U2AF1 and ASXL1 mutations. Moreover, ETV6mut was associated with a lower complete remission (CR) rate (45.8% vs. 69.1%, P = 0.015) and shorter OS (P = 0.048) compared to the ETV6 wild-type (ETV6wt) group. Notably, the achievement of CR did not contribute to survival benefit in AML with ETV6mut. In multivariate analysis, ETV6 mutation was shown to be an independent adverse factor for OS in AML patients (HR: 1.72, 95% CI: 1.03–2.89; P = 0.040). Taken together, our study shows a mutational profile of ETV6 in AML and suggests that ETV6 mutations are associated with poor prognosis in AML patients.