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
Splicing factor 3B subunit 1 (SF3B1) is a complex takes part in intron splicing of pre-mRNA and mutations within it have been reported frequently in myeloid malignancies including myelodysplastic syndromes (MDS). However, its prognostic value has been controversial. Hence, we aimed this meta-analysis to investigate the prognostic effect of SF3B1 mutations in patients with MDS. Several electronic databases were searched in of EMBASE, PubMed, the Cochrane Library and Web of Science (published up to November 2017) to obtain eligible studies. The pooled Hazard Ratio (HRs) and 95% confidence interval (CI) for overall survival (OS) and leukemia-free survival (LFS) as the primary and secondary endpoint, respectively, were chosen and extracted to determine the prognostic impact of SF3B1 mutations and to compare SF3B1 mutations to those with wild-type. Nine cohort studies with a total of 2259 patients were obtained, and the pooled HRs for OS was 0.93 (95% CI: 0.56-1.52, p-value = 0.78) and revealed no significant effect on overall survival of MDS patients by random effect models. Our meta-analysis suggested that SF3B1 has no impact on OS of patients with MDS, however, an adequately designed prospective study with a large number of patients with different type of SF3B1 mutations is needed to confirm these results. Additionally, Begg's and Egger's tests did not show any publication bias.
