Correlation between epigenetic modifier gene mutations and prognosis of patients with acute lymphoblastic leukemia: a systematic review and meta-analysis

Abstract

Objectives: The impact of epigenetic modifier gene mutations (EMMs) on the prognosis of patients with acute lymphoblastic leukemia (ALL) is controversial, which is unlike AML. A meta-analysis is needed to evaluate the prognostic value of EMMs in ALL. Methods: Three databases, including PubMed, EMBase and Web of Science, were retrieved to find out studies exploring the association of EMMs and survival outcomes in ALL. Pooled hazard ratios (HRs) and 95% confidential interval (95%CI) were used to assess the impact of EMMs. Results: Nineteen studies were included in our meta-analysis. DNMT3A mutation was an adverse prognostic factor in overall survival (OS) in patients with ALL (HR, 4.143; P< 0.001) as well as adult T-ALL patients (HR, 3.746; P< 0.001) and those with early T-ALL (HR, 3.523; P= 0.001). IDH mutation also had an unfavorable impact on OS in ALL (HR, 3.583; P< 0.001) and adult T-ALL cohort (HR, 3.562; P< 0.001). For pediatric patients, mutant PHF6 was significantly associated with worse OS in both B-ALL (HR, 3.194; P = 0.026) and T-ALL (HR, 2.125; P = 0.033), while PHF6 mutation had no prognostic impact on the survival of adult T-ALL patients. In addition, patients with KMT2A mutation had shorter OS compared to those with wild type (HR, 4.605; P = 0.045), whereas other EMMs had no impact on prognosis in any type of ALL. Conclusions: Mutations in DNMT3A, IDH, PHF6 and KMT2A showed a significant prognostic effect in ALL or in its specific subtypes, which might contribute to risk stratification and treatment guidance in the management of ALL patients.