Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis

Background: The ATM protein acts as an essential part of the signal transduction pathway upstream of p53 which activates following induction of DNA double-strand breaks (DSBs) and leads to transcriptional proapoptotic genes activation that synchronizes DNA repair. Aim: Several studies have assessed the relationship between ATM mutations and the clinical prognosis in patients with chronic lymphocytic leukemia (CLL). However, its prognostic value has not yet been fully clarified. Hence, we aimed this meta-analysis to investigate the prognostic effect of ATM mutations in patients with CLL. Method: The selected clinical studies were extracted from various electronic databases such as PubMed, EMBASE, the Cochrane Library, and Web of Science. In our meta-analysis, Hazard Ratio (HRs) and 95 % confidence interval (CI) for overall survival (OS) were chosen to estimate the prognostic impact of ATM mutations and to compare ATM mutations to those with wild-type. Results: A total of 1299 patients from seven studies were collected. The pooled HRs for OS recommended that patients with CLL had a poorer prognosis HR = 1.24 (95 % CI: 0.97-1.59). The incidence of ATM mutations was found 15.8 % in patients with CLL. Begg's and Egger's tests did not show any significant bias between studies. Conclusion: In conclusion, this meta-analysis indicated that ATM mutations were significantly associated with adverse prognostic effect in patients with CLL. However, a randomized controlled prospective study with a large number of patients with different types of ATM mutations is required to assert these results.