Prognostic impact of IL7R mutations on acute myeloid leukemia

Abstract

Background: Interleukin-7 receptor ( IL7R) mutation has been demonstrated to be an adverse prognostic factor in acute lymphoblastic leukemia (ALL) patients. However, the effects of the IL7R mutation on acute myeloid leukemia (AML) have rarely been reported. Here, we investigated IL7R mutations and their effects on AML patients. Methods: A total of 346 newly diagnosed AML patients from January 2017 to July 2020 at Nanfang Hospital were analyzed in this study. A genomic panel of 167 gene targets was detected by next-generation sequencing. Results: Among 346 patients, 33 (9.5%) AML patients carried IL7R mutations. With a median follow-up of 50.7 months (95% confidence interval (CI) 17.3–62.2), the 5-year overall survival (OS) rates were 51.5% (95% CI 37.0%–71.0%) and 72.2% (95% CI 67.4%–77.3%; p = 0.008), the 5-year event-free survival (EFS) rates were 36.1% (95% CI 23.2%–57.1%) and 58.1% (95% CI 52.9%–63.8%; p = 0.005), the 5-year non-relapse mortality (NRM) were 21.4% (95% CI 8.5%–38.2%) and 6.2% (95% CI 3.7%–9.5%; p = 0.004) in the IL7R mutant ( IL7R MUT) group and non-IL7R mutant ( IL7R WT) group, respectively. There is no significant difference in the disease-free survival (75.1% vs 73.5%, p = 0.885) and cumulative incidence of relapse (25.7% vs 25.2%, p = 0.933) between IL7R MUT and IL7R WT group. Furthermore, patients who underwent hematopoietic stem cell transplantation (HSCT) still had more adverse outcomes in the IL7R MUT group than in the IL7R WT group (5-year OS: 61.9% vs 85.3%, p = 0.003). In the TET2 ( p = 0.013) and DNA methyltransferase 3A ( DNMT3A; p = 0.046) mutation subgroups, the presence of IL7R mutations was associated with worse OS than in AML patients without IL7R mutations. Conclusion: Our study demonstrated that the IL7R mutation is associated with an inferior prognosis for AML patients. Patients with IL7R mutations have higher NRM, shorter OS, and EFS than patients without IL7R mutations, even patients who have undergone HSCT. Future larger and multicentric prospective studies will be explored.