ABSTRACT
Understanding the underlying mechanism of acute myeloid leukemia (AML) has led to the discovery of novel biomarkers to help predict, treat and monitor leukemia. DNA (cytosine-5)-methyltransferase 3 A (DNMT3A) is considered a prognostic and therapeutic epigenetic target in AML patients with a hotspot mutation of R882. R882 mutation is associated with impaired differentiation of Hematopoietic stem cells in the bone marrow and disease progression. The prevalence of R882 mutation varied in different ethnicities and countries, and similarly, its prognostic impact differed among numerous studies. Nevertheless, the co-occurrence of mutations in R882 with NPM1 and FLT3 has been reported more frequently and is associated with a worse prognosis. These studies also suggest diverse results regarding bone marrow transplantation response as a treatment, while chemoresistance is reached as a conclusive outcome These findings highlight the crucial need for an in-depth discussion on the significance of the R882 mutation in AML patients. Understanding its impact on leukemic transformation, prognosis, and treatment is vital for advancing clinical implications.
ABSTRACT
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.
